Latest Research

  • Perspective |

    Glucose-responsive insulin is a therapeutic that modulates its potency, concentration or dosing relative to a patient’s dynamic glucose concentration. This Perspective summarizes some of the recent accomplishments in this field as well as discussing new computational algorithms that may aid in the development of such therapeutics.

    • Naveed A. Bakh
    • , Abel B. Cortinas
    • , Michael A. Weiss
    • , Robert S. Langer
    • , Daniel G. Anderson
    • , Zhen Gu
    • , Sanjoy Dutta
    •  & Michael S. Strano
  • Article |

    Determining the structure­–activity relationships for complex structures can be quite challenging, but it is often the method by which many natural products are optimized for use as drugs. Now, the combination of a fluoroaryl borane catalyst, a phosphine additive and a silane reducing agent enables the late-stage selective modification of complex bioactive natural products in order to provide rapid access to a wide array of structures, and therefore functions.

    • Trandon A. Bender
    • , Philippa R. Payne
    •  & Michel R. Gagné
  • Article |

    Rationally designed arrays of hydrogen bonds between aromatic oligoamide segments have now been shown to generate abiotic helix-turn-helix and unexpected dimeric and trimeric helix bundle motifs. These structures show kinetic and thermodynamic stability, and cooperative folding in nonpolar solvents.

    • Soumen De
    • , Bo Chi
    • , Thierry Granier
    • , Ting Qi
    • , Victor Maurizot
    •  & Ivan Huc
  • Article |

    The biosynthesis of secondary metabolites such as stephacidin A and its congeners continues to intrigue both biochemists and synthetic chemists. Now, a laboratory chemical synthesis of these natural products has been achieved based on a bioinspired synthetic strategy, which may provide key insights into the possible biosynthesis of these captivating molecules.

    • Ken Mukai
    • , Danilo Pereira de Sant'Ana
    • , Yasuo Hirooka
    • , Eduardo V. Mercado-Marin
    • , David E. Stephens
    • , Kevin G. M. Kou
    • , Sven C. Richter
    • , Naomi Kelley
    •  & Richmond Sarpong
  • Article |

    Providing detailed structural descriptions of the ultrafast photochemical events that occur in light-sensitive proteins is key to their understanding. Now, excited-state structures in the reversibly switchable fluorescent protein rsEGFP2 have been solved by time-resolved crystallography using an X-ray laser. These structures enabled the design of a mutant with improved photoswitching quantum yields.

    • Nicolas Coquelle
    • , Michel Sliwa
    • , Joyce Woodhouse
    • , Giorgio Schirò
    • , Virgile Adam
    • , Andrew Aquila
    • , Thomas R. M. Barends
    • , Sébastien Boutet
    • , Martin Byrdin
    • , Sergio Carbajo
    • , Eugenio De la Mora
    • , R. Bruce Doak
    • , Mikolaj Feliks
    • , Franck Fieschi
    • , Lutz Foucar
    • , Virginia Guillon
    • , Mario Hilpert
    • , Mark S. Hunter
    • , Stefan Jakobs
    • , Jason E. Koglin
    • , Gabriela Kovacsova
    • , Thomas J. Lane
    • , Bernard Lévy
    • , Mengning Liang
    • , Karol Nass
    • , Jacqueline Ridard
    • , Joseph S. Robinson
    • , Christopher M. Roome
    • , Cyril Ruckebusch
    • , Matthew Seaberg
    • , Michel Thepaut
    • , Marco Cammarata
    • , Isabelle Demachy
    • , Martin Field
    • , Robert L. Shoeman
    • , Dominique Bourgeois
    • , Jacques-Philippe Colletier
    • , Ilme Schlichting
    •  & Martin Weik
  • Article |

    A 335 base-pair gene encoding the green fluorescent protein iLOV and an epigenetically modified variant have now been assembled by click-DNA ligation of ten functionalized oligonucleotides. The resulting fully synthetic gene contained eight triazoles at the sites of chemical ligation, yet the synthetic gene was shown to be fully biocompatible in Escherichia coli.

    • Mikiembo Kukwikila
    • , Nittaya Gale
    • , Afaf H. El-Sagheer
    • , Tom Brown
    •  & Ali Tavassoli
  • Article |

    Singlet fission — the conversion of one singlet exciton into two triplet excitons, could improve the efficiency of photovoltaic devices — but its mechanism is still to be fully understood. Now, in films of TIPS-tetracene, it has been shown that the formation of the triplet pair state, which has been proposed to mediate singlet fission, is ultrafast and vibronically coherent in this endothermic fission system.

    • Hannah L. Stern
    • , Alexandre Cheminal
    • , Shane R. Yost
    • , Katharina Broch
    • , Sam L. Bayliss
    • , Kai Chen
    • , Maxim Tabachnyk
    • , Karl Thorley
    • , Neil Greenham
    • , Justin M. Hodgkiss
    • , John Anthony
    • , Martin Head-Gordon
    • , Andrew J. Musser
    • , Akshay Rao
    •  & Richard H. Friend
  • Article |

    Two important properties in an activated chemical reaction are the barrier height and its geometrical dependence. Now, a method has been developed to directly map the angle-dependent barrier to reaction from polarized scattering data for the Cl + CHD3 reaction. The method should be applicable to many other direct reactions with a colinear barrier.

    • Huilin Pan
    • , Fengyan Wang
    • , Gábor Czakó
    •  & Kopin Liu
  • Article |

    Crystals are typically thought to be brittle and fragile materials, but needles of copper(II) acetylacetonate have now been shown to be flexible enough to be reversibly tied into a knot. Mechanistic investigations using synchrotron X-ray diffraction determined that the elastic bending occurs through rotation of the molecules within the crystal lattice.

    • Anna Worthy
    • , Arnaud Grosjean
    • , Michael C. Pfrunder
    • , Yanan Xu
    • , Cheng Yan
    • , Grant Edwards
    • , Jack K. Clegg
    •  & John C. McMurtrie
  • Article |

    Two coordination cages have been devised that undergo covalent modification during a cascade of two orthogonal Diels–Alder reactions. This results in increased lipophilicity for the second cage, enabling its phase transfer and separation from the first. The trigger, relay and inhibition features of this cascade system mimic key aspects of natural post-translational modification cascades.

    • Ben S. Pilgrim
    • , Derrick A. Roberts
    • , Thorsten G. Lohr
    • , Tanya K. Ronson
    •  & Jonathan R. Nitschke
  • Article |

    Despite advances in peptide synthesis techniques, explicit control over the quaternary structure of synthetic peptides has remained elusive. Now, the dynamic covalent chemistry of hydrazide- and aldehyde-containing peptides has now been shown to enable the formation of unique quaternary structures with topological diversity. Using this method, oligomers were assembled into complex structures showing dramatic enhancements of antimicrobial effectiveness versus Staphylococcus Aureus.

    • James F. Reuther
    • , Justine L. Dees
    • , Igor V. Kolesnichenko
    • , Erik T. Hernandez
    • , Dmitri V. Ukraintsev
    • , Rusheel Guduru
    • , Marvin Whiteley
    •  & Eric V. Anslyn
  • Article |

    The first demonstration of a protein designed entirely from first principles that binds a small-molecule cofactor in a precisely predetermined orientation has now been described. The design method utilizes a remote protein core that both anchors and predisposes a flexible binding site for the desired cofactor-binding geometry.

    • Nicholas F. Polizzi
    • , Yibing Wu
    • , Thomas Lemmin
    • , Alison M. Maxwell
    • , Shao-Qing Zhang
    • , Jeff Rawson
    • , David N. Beratan
    • , Michael J. Therien
    •  & William F. DeGrado
  • Article |

    Polyoxygenated aliphatic chains with multiple hydroxyl groups are common in a wide array of compounds, often with potent biological activity. Now, a new ruthenium catalyst enables selective dehydrogenation of a single hydroxyl group in a broad scope of complex polyols. This site-selective modification facilitates the rapid incorporation of nitrogen-based functional groups into diverse natural products.

    • Christopher K. Hill
    •  & John F. Hartwig
  • Article |

    Chemically termolecular reactions — arising from the collision of ephemeral collision complexes with other chemically reactive species — have been neglected in current gas-phase chemical mechanisms of combustion and planetary atmospheres. First principles calculations reveal that such chemically termolecular reactions constitute major pathways affecting macroscopic observables.

    • Michael P. Burke
    •  & Stephen J. Klippenstein
  • Article |

    Intercalation — a cornerstone of materials science with wide-ranging applications — has now been demonstrated in a superatomic crystal. A redox-active tetracyanoethylene guest was inserted into the lattice of a material consisting of alternate layers of {Co6Te8} clusters and C60 fullerenes, leading to a single-crystal-to-single-crystal transformation that significantly modulates the material's optical and electrical transport properties.

    • Evan S. O'Brien
    • , M. Tuan Trinh
    • , Rose L. Kann
    • , Jia Chen
    • , Giselle A. Elbaz
    • , Amrita Masurkar
    • , Timothy L. Atallah
    • , Maria V. Paley
    • , Nilam Patel
    • , Daniel W. Paley
    • , Ioannis Kymissis
    • , Andrew C. Crowther
    • , Andrew J. Millis
    • , David R. Reichman
    • , X.-Y. Zhu
    •  & Xavier Roy
  • Article |

    Although samarium-mediated cyclizations have the potential to generate significant molecular complexity, historically it has not proven possible to exert enantiocontrol through the use of a chiral ligand in complex product synthesis. Now, an enantioselective SmI2-mediated radical cyclization has been developed using a chiral aminodiol ligand. Desymmetrizing 5-exo ketyl-alkene cyclizations and cyclization cascades of unsaturated ketoesters deliver complex products and typically proceed with high enantioselectivity and diastereoselectivity.

    • Nicolas Kern
    • , Mateusz P. Plesniak
    • , Joseph J. W. McDouall
    •  & David J. Procter
  • Article |

    Catalysis involving high-valent metals is an important facet of modern chemistry, but tools for catalyst development in this field have lagged behind those for low-valent systems. Now, an experimental system that can accurately model and predict reactivity has been developed to aid high-valent catalyst design.

    • Brennan S. Billow
    • , Tanner J. McDaniel
    •  & Aaron L. Odom
  • Article |

    Mononuclear gold(II) complexes are very labile (and thus very rare) species. Now, a gold(II) porphyrin complex has been isolated and characterized, and its reactivity towards dioxygen, nitrosobenzene and acids investigated. Owing to a second-order Jahn–Teller distortion, the gold atoms were found to adopt a 2+2 coordination mode in a planar N4 environment.

    • Sebastian Preiß
    • , Christoph Förster
    • , Sven Otto
    • , Matthias Bauer
    • , Patrick Müller
    • , Dariush Hinderberger
    • , Haleh Hashemi Haeri
    • , Luca Carella
    •  & Katja Heinze
  • Article |

    Interest in surface-mediated chemistry has led to the design of small molecule models for surfaces, which provide mechanistic insight and have practical applications. Now, the cooperative behaviour of five nickel centres has been shown to provide reactivity reminiscent of highly active metal surface sites, leading to carbon-atom abstraction from alkenes under ambient conditions.

    • Manar M. Shoshani
    •  & Samuel A. Johnson
  • Article |

    Bacterial naphthoquinone meroterpenoid natural products defy biosynthetic logic via classical biochemical paradigms. Now, an enzyme promoted α-hydroxyketone rearrangement catalysed by vanadium-dependent haloperoxidases reveals a conserved biosynthetic reaction in this molecular class that further has inspired a concise biomimetic synthesis of naphthomevalin, a prominent member of the napyradiomycin meroterpenes.

    • Zachary D. Miles
    • , Stefan Diethelm
    • , Henry P. Pepper
    • , David M. Huang
    • , Jonathan H. George
    •  & Bradley S. Moore
  • Article |

    A chemical proteomic strategy has now been reported for the global profiling of lysine reactivity and ligandability. Using this approach, >9000 lysines in the human proteome were evaluated, leading to the discovery of hyper-reactive lysines, and lysines that can be targeted by electrophilic small molecules to perturb enzyme function and protein–protein interactions.

    • Stephan M. Hacker
    • , Keriann M. Backus
    • , Michael R. Lazear
    • , Stefano Forli
    • , Bruno E. Correia
    •  & Benjamin F. Cravatt
  • Article |

    Delayed resolution of G-quadruplexes during replication can induce localized loss of epigenetic information and changes in gene expression. Now, this effect has been used to discover biologically potent G-quadruplex ligands and to demonstrate that G-quadruplex stabilization can induce epigenetic changes that are heritable across cell divisions even after the ligand is removed.

    • Guillaume Guilbaud
    • , Pierre Murat
    • , Bénédicte Recolin
    • , Beth C. Campbell
    • , Ahmed Maiter
    • , Julian E. Sale
    •  & Shankar Balasubramanian
  • Article |

    Realization of the bicyclic aromaticity has attracted much attention because of the potential to modulate the fundamental properties of 3D aromatic organic molecules that are not topologically planar. Now, the synthesis and characterization of dual-aromatic molecules, and their electronically mixed [4n+1]/[4n+1] triplet bi-radical species displaying Baird-type aromaticity, has been realized.

    • Won-Young Cha
    • , Taeyeon Kim
    • , Arindam Ghosh
    • , Zhan Zhang
    • , Xian-Sheng Ke
    • , Rashid Ali
    • , Vincent M. Lynch
    • , Jieun Jung
    • , Woojae Kim
    • , Sangsu Lee
    • , Shunichi Fukuzumi
    • , Jung Su Park
    • , Jonathan L. Sessler
    • , Tavarekere K. Chandrashekar
    •  & Dongho Kim