Articles in 2011

Nitrogen-containing heterocycles are ubiquitous in natural products, pharmaceuticals and in materials science. Here, the stereoselective synthesis of a wide array of structurally diverse, functionalized lactams by palladium-catalysed enantioselective enolate alkylation is described.

Poly(ethylene glycol) conjugates have been widely used to improve the stability of proteins for use as therapeutics, but this stability comes at the expense of binding affinity. Here, poly(carboxybetaine) — a zwitterionic polymer — is shown to provide increased stability while also enhancing binding due to its super-hydrophilic nature.

Adsorbed carbon monoxide typically acts to poison the oxidation of alcohols on heterogeneous catalysts and electrocatalysts. Here, it is shown that carbon monoxide that has been adsorbed irreversibly on a Au(111) surface can act as a promoter for this process by enhancing the scission of C–H bonds in the alcohol to yield the corresponding aldehyde.

A general reaction-discovery platform has been used for identification of a new multicomponent transformation. The approach entails rapid analysis of interfacial chemical reactions on arrays of self-assembled monolayers using mass spectrometry. This enabled identification of a simple organic phosphine that catalyses a previously unknown condensation of siloxy alkynes, aldehydes and amines.

A designed metalloprotein containing an Hg(II) trithiolate centre that provides structural stability, and a Zn(II) tris histidine centre serving as a catalytic mimic of carbonic anhydrase, is shown to display rates that are comparable to the natural enzyme for ester hydrolysis and CO₂ hydration.

The self-assembly of monometallic moieties with organic ligands has proved to be a highly versatile approach for preparing a range of metal–ligand assemblies that are helical, optically pure and stable in aqueous solutions. One such iron(II) ‘flexicate’ system exhibits significant interactions with DNA, as well as promising antimicrobial activity properties.

Assembling random networks on a surface is an intriguing — and potentially useful — phenomenon, but partial order is difficult to control. Researchers have now altered two-dimensional tetracarboxylic acid networks through only small chemical changes. This phase behaviour reveals that entropy, alongside energy, plays a crucial role in the order–disorder balance.

‘Roaming’ is a recently discovered reaction dynamics phenomenon in which a molecule undergoes frustrated dissociation to radicals, followed by an intramolecular abstraction reaction. An imaging study, with associated high-level ab initio calculations, has now shown that ‘roaming-mediated isomerization’ plays a key role in the photodissociation of nitrobenzene.

The design and synthesis of a family of chiral and conformationally constrained oligomers is described. Asymmetric synthesis of the monomers is presented and the preparation of a 160,000-member library of diverse tetramers via split-and-pool methods is discussed. From this library, a non-covalent ligand to the DNA-binding domain of p53 was discovered.

Despite their potential roles in catalysis and materials science, the redox-induced dynamic structural changes in (sp²-carbon ligand)–(multiple metals)–(sp²-carbon ligand) systems are not well understood. Now, tetra-palladium sandwich complexes have been described that exhibit redox-switchable assembly of the metal centres or coupling of the ligands.

One-dimensional wires with metal–metal bonding have been studied for more than a century, but control over structure and properties has remained challenging. Here, palladium–palladium bonding is used to make one-dimensional wires with lengths of up to 750 nm in solution, whose molecular structures can be rationally modified.

The reversible covalent binding of mono-alcohols with high affinity is challenging because of their poor nucleophilicity. A multi-component assembly has now been used to achieve reversible binding of secondary alcohols through iminium activation and product stabilization. Moreover, such assemblies can be used to determine alcohol chirality and enantiomeric excess.

Colloidal hybrid nanoparticles represent an emerging class of multifunctional artificial molecules. However, unlike actual molecules, their complexity is limited by the lack of a mechanism-driven design framework. Here, nanoparticle analogues of chemoselectivity, regiospecificity, molecular substituent effects, and coupling reactions are used to predictably synthesize hybrid nanoparticle trimers, tetramers, and oligomers.

Chemists are able to prepare a wide variety of metal–organic frameworks by connecting together inorganic and organic building blocks of all sorts of shapes and properties. Now, a large-scale computational screening approach that simulates thousands of hypothetical MOFs from previously synthesized ones can help identify just which materials should be pursued.

The most complex non-DNA molecular knot prepared so far is self-assembled around a chloride anion from five metal cations, five bis-aldehyde and five bis-amine building blocks, in a one-pot reaction. The X-ray crystal structure of the 160-atom-loop pentafoil knot reveals a symmetrical closed-loop double helicate with a chloride anion held at its centre by ten CH···Cl⁻ hydrogen bonds.

The taxane diterpene family is structurally complex and exhibits a wide range of biological activities, best exemplified by the successful drug Taxol. Here, two of the least oxidized taxanes in the family, ‘taxadienone’ and taxadiene, are prepared by total synthesis on a gram scale. The concise synthetic route described herein provides a scalable, enantioselective entry to the taxane family of natural products.

The fastest catalysts in nature for producing and oxidizing hydrogen are [FeFe]-hydrogenases, which make use of an extra one-electron redox equivalent from an iron-sulfur cluster that is outside the core. Now, a ferrocene-based ligand that oxidizes at mild potential performs this cluster's role in an excellent synthetic hydrogenase model.

Non-coding RNAs are ubiquitous biomolecules with intricate three-dimensional folds that are difficult to characterize. This Article presents an information-rich strategy for inferring RNA structure by combining nucleotide-by-nucleotide mutagenesis with single-nucleotide-resolution chemical mapping.

Intracellular biothiols can degrade nanoparticle monolayers, compromising the function of these potentially promising tools. Here, we describe a label-free method for quantifying the intracellular stability of quantum dot monolayers, using laser desorption/ionization mass spectrometry coupled with inductively coupled plasma mass spectrometry.

Cell-laden synthetic hydrogels — formed via a copper-free click reaction between a poly(ethylene glycol) tetra-cyclooctyne and a peptide-diazide — provide a platform to investigate the cells' response to various stimuli during growth. The hydrogel's biochemical aspects are readily controlled by a thiol-ene photocoupling reaction initiated with visible light, whereas the biomechanical properties of the network are altered via a UV-mediated photodegradation.