Articles in 2013

Mechanistic studies of reductive elimination that forms aryl–aryl bonds from simple mono- and dinuclear gold phosphine complexes are disclosed. The observed rates for reductive elimination are unusually fast, even at temperatures as low as –52 °C, providing insight into the fundamental reactivity of oxidized organogold complexes.

Chemical validation of new drug targets is urgently required to help develop new antimalarial therapies. Here, chemical proteomic tools and selective enzyme inhibitors are combined to study protein lipidation in human malaria parasites, leading to in vitro and in vivo validation of the enzyme N-myristoyltransferase as a drug target.

Polynitrogen compounds are of interest on a fundamental level and as potential high-energy-density materials. A crystalline solid that consists of two isomeric forms of N₈ molecules held together by weak van der Waals interactions has now been predicted to exist, and to be stable even at low pressures.

Graphene oxide sheets hold promise for a variety of applications but are disordered and inhomogeneous on synthesis. Although processes to resolve this exist they typically remove oxygen groups, affecting the sheets’ properties. Now, a scalable, mild thermal annealing procedure has been devised that enhances the optical and electronic properties of graphene oxide sheets through phase transformation, while preserving their oxygen functionality.

Two milliseconds of molecular dynamics simulations of a major drug-target G-protein-coupled receptor (GPCR) has been carried out using Google's Exacycle cloud computing platform. Markov state models were used to aggregate independent simulations into a statistical model that provides an atomistic description of GPCR ligand-modulated activation pathways.

Identification of glycosylation patterns is complicated by the lack of sensitive analytical techniques that can distinguish between epimeric carbohydrates. It has now been shown that ion-mobility tandem mass spectrometry of ions derived from glycopeptides and oligosaccharides enables glycan stereochemistry to be determined, highlighting the potential of this technique for sequencing complex carbohydrates on cell surfaces.

Liquid-phase-processable graphene nanoribbons (GNRs) over 200 nm long and with well-defined structures have now been synthesized by a bottom-up method, and are found to have a large optical bandgap of 1.88 eV. Scanning probe microscopy revealed highly ordered self-assembled monolayers of the GNRs, and the high intrinsic charge-carrier mobility of individual ribbons was characterized by terahertz spectroscopy.

The rate of an intramolecular hydrogen transfer reaction in a single porphycene molecule resting on a copper surface can be controlled by placing a copper adatom close to it. Cooperativity effects are also observed in rows of porphycene molecules, where the reaction rate of each individual molecule depends on the precise tautomer state of its neighbours.

The presence of RNA G-quadruplex structures in human cells using a structure-specific antibody is demonstrated. Using small molecules, the selective stabilization of cytoplasmic RNA G-quadruplexes versus nuclear DNA G-quadruplexes is demonstrated. These findings validate the existence of RNA G-quadruplexes and their specific targeting by small molecules within a cellular context.

HIV-1 replication is inhibited by the enzyme APOBEC3G via two separate mechanisms. A deamination mechanism requires rapid binding and release of single-stranded DNA (ssDNA), whereas a roadblock mechanism requires slow binding. Now APOBEC3G has been shown to initially bind ssDNA with rapid on–off rates. The enzyme subsequently converts via oligomerization to a slowly dissociating binding mode, which, it is proposed, inhibits reverse transcription.

A palladium-catalysed, highly enantio- and diastereoselective [3 + 2] cycloaddition reaction to produce densely functionalized pyrrolidine frameworks is developed by exploiting a new phosphine ligand with a chiral ammonium salt component. Rigorous control of the individual absolute stereochemistry of three contiguous stereocentres, including vicinal all-carbon quaternary stereocentres, is possible using this methodology.

Emulating the biogenesis of natural products, a synthetic strategy is described in which an achiral multipotent intermediate reacts through three distinct [4 + 2] cyclizations and two types of redox-mediated annulation. This results in divergent access to natural product-like scaffolds in 6–9 steps. The efficiency of this approach is highlighted in the total syntheses of three natural products.

Singlet exciton fission produces two triplet excited states from one excited singlet through interchromophoric coupling, which is thought to require local order. Now, a triplet yield of 200% and diffusion-limited triplet formation are reported in solutions of TIPS pentacene. Kinetic studies revealed an excimer intermediate and enabled suggestions of design principles for the promotion of singlet fission.

The ability to self-heal is an important survival feature in nature, with in-built systems working to correct faults and extend the lifetimes of organisms. Now, self-healing chemistry has been applied to overcome the short cycling lifetime of high-capacity rechargeable lithium-ion batteries with silicon-microparticle anodes that suffer from mechanical fractures.

An aryne intermediate produced by a hexadehydro-Diels–Alder reaction is shown to engage in an unusual — and before this work rare and inefficient — aromatic ene reaction to produce an isotoluene. This second reactive intermediate can then engage an external enophile resulting in a conjunctive cascade in which four C–C bonds and three rings are created without involvement of reagents or generation of by-products.

Multifunctional catalysts typically process substrates and intermediates concurrently. Here, a strategy is described to separate catalytic activities in the time domain (temporal separation). Application of this strategy has led to the development of a method to effect the anti-Markovnikov reductive functionalization of terminal alkynes; such an approach may facilitate the development of other synthetic reaction cascades.

Bacteria use signalling networks to control population behaviour. Here it is shown that polymers that promote clustering of bacteria can influence bacterial signalling and induce unexpected responses in quorum-sensing-controlled phenotypes. These responses can be better modulated by controlling the affinity of the polymer to both bacteria and signalling molecules.

Despite their appearance in a number of bioactive natural products, the synthesis of 5-membered carbocycles has received much less attention than synthesis of their 6-membered counterparts. Here, a Michael-aldol-β-lactonization cascade is used to forge two C-C bonds, one C-O bond, two rings and up to three contiguous stereocentres and deliver complex cyclopentanes with high levels of relative and absolute stereocontrol.

Attractive van der Waals dispersion forces have been implicated in mechanisms as diverse as gecko adhesion and anaesthesia. Now, it has been found using synthetic molecular balances that dispersion forces between alkyl chains are an order of magnitude weaker in solution than they are in the gas phase.

Molecular self-replication through ribozyme-catalysed RNA synthesis could shed light on the origins of life. Here, a polymerase ribozyme capable of synthesizing an RNA sequence longer than itself is described, based on a cold-adapted ribozyme variant evolved in ice. This process demonstrates the potential for the emergence of novel ribozyme phenotypes in altered reaction environments.