Volume 9 Issue 12, December 2017

Volume 9 Issue 12

The de novo design of a protein capable of binding a cofactor in a unique orientation is a challenging problem because a range of structurally similar, yet different, complexes are often formed. Now, a team led by David N. Beratan, Michael J. Therien and William F. DeGrado report a protein — designed entirely from first principles — that binds a small-molecule cofactor in a unique and precisely predetermined orientation (shown schematically on the cover). Solving this puzzle required the design of a remote protein core that predisposes a flexible binding site to accommodate the porphyrin cofactor in a unique binding geometry.Article p1157IMAGE: NICHOLAS POLIZZICOVER DESIGN: TULSI VORALIA

News and Views

  • News & Views |

    Building materials with clusters instead of atoms promises unconventional properties, but those 'superatomic solids' are often too fragile to manipulate. Now, intercalating a guest within an ionic layered solid made of fullerenes and metal chalcogenide clusters greatly alters its conductivity and optical properties without disrupting its crystalline structure.

    • Shiv N. Khanna
    •  & Arthur C. Reber
  • News & Views |

    Non-covalent interactions can organize planar molecules into two-dimensional arrays. It has now been shown that such arrays can be combined at the solid–liquid interface into bilayered heterostructures.

    • Manfred Buck
  • News & Views |

    The use of mechanical force to break and build chemical bonds in polymers can enable transformations that cannot be conducted using stimuli such as light and heat. Now, an insulating polymer has been mechanically unzipped to create a semiconducting polymer with extended regions of conjugation.

    • Stephen L. Craig

Articles

  • 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 |

    The collective synthesis of several oligomeric polypyrroloindoline natural products, including hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridines B and C, is accomplished through the iterative action of an asymmetric small molecule copper catalyst. This strategy also enables the synthesis of putatively unnatural quadrigemine H-type isomers.

    • Christopher R. Jamison
    • , Joseph J. Badillo
    • , Jeffrey M. Lipshultz
    • , Robert J. Comito
    •  & David W. C. MacMillan
  • 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 |

    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 |

    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 |

    Supramolecular heterostructures have been formed by the sequential deposition of two molecular layers with different symmetries and lattice constants — one consisting of carboxylic acid, the other of cyanuric acid and melamine — on a hexagonal boron nitride substrate. Characterization by atomic force microscopy and molecular dynamics simulations shows epitaxial arrangements between the layers.

    • Vladimir V. Korolkov
    • , Matteo Baldoni
    • , Kenji Watanabe
    • , Takashi Taniguchi
    • , Elena Besley
    •  & Peter H. Beton
  • 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 |

    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 |

    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 |

    Modular hybridization probes (M-Probes) have been developed that enable sequence-selective binding of complex nucleic acid targets. The M-probes can target sequences that: are hypervariable at prescribed loci, are long continuous sequences of over 500 nucleotides, or contain repetitive sequences. A hybrid-capture assay using the M-probes was developed that was capable of determining the exact triplet repeat expansion number in the Huntington's gene from genomic DNA.

    • Juexiao Sherry Wang
    • , Yan Helen Yan
    •  & David Yu Zhang
  • Article |

    Current mineral-based theories do not fully address how enzymes emerged from prebiotic catalysts. Now, iron–sulfur clusters can be synthesized by UV-light-mediated photolysis of organic thiols and photooxidation of ferrous ions. Iron–sulfur peptides may have formed easily on early Earth, facilitating the emergence of iron–sulfur-cluster-dependent metabolism.

    • Claudia Bonfio
    • , Luca Valer
    • , Simone Scintilla
    • , Sachin Shah
    • , David J. Evans
    • , Lin Jin
    • , Jack W. Szostak
    • , Dimitar D. Sasselov
    • , John D. Sutherland
    •  & Sheref S. Mansy
  • 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 |

    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
  • 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 |

    X-ray and neutron diffraction studies, in conjunction with quantum chemical techniques, have been used to define a new oxidative bond activation pathway that involves simultaneous activation of both bonds of a β-diketiminate-stabilized GaH2 unit at a single metal centre.

    • Joseph A. B. Abdalla
    • , Alexa Caise
    • , Christian P. Sindlinger
    • , Rémi Tirfoin
    • , Amber L. Thompson
    • , Alison J. Edwards
    •  & Simon Aldridge
  • Article |

    Octameric complexes of serine are long known for their special properties, such as their enhanced stability and preference for homochirality. Yet, there is no consensus on their structures. Now, experimental data on the serine octamer–dichloride complex is presented that supports a highly symmetrical, highly stable structure.

    • Jongcheol Seo
    • , Stephan Warnke
    • , Kevin Pagel
    • , Michael T. Bowers
    •  & Gert von Helden
  • Article |

    Amines are commonly occurring units in many biologically active molecules. Now, a catalytic method has been developed that merges an unprotected/unactivated ketimine, a monosubstituted allene and a commercially available diboron reagent to afford versatile α-tertiary amines in up to 95% yield, >98% diastereomeric ratio and >99:1 enantiomeric ratio. The utility of this method was demonstrated through its application to the synthesis of the tricyclic core of a class of compounds with anti-Alzheimer activity.

    • Hwanjong Jang
    • , Filippo Romiti
    • , Sebastian Torker
    •  & Amir H. Hoveyda
  • 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 |

    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

In Your Element

  • In Your Element |

    Named after a mysterious place, thulium — one of the rarest rare earths — has some exotic chemistry in store for us, says Polly Arnold.

    • Polly Arnold

Retraction