Volume 4 Issue 2, February 2012

The design of a small-molecule library for drug discovery attempts to combine the favourable diversity of natural product structures with the modularity of peptide synthesis.

Valuable insight into the use of lasers to control electron dynamics can be gained by simulations, but these are often limited by the uncertainty in the model systems used. Now, accurate calculations of controlled electron motion in benzene improve on this, while showing that its aromaticity could potentially be 'switched off'.

Stacking of a chromophoric molecule in the solid state has been altered rationally by the formation of co-crystals, allowing fine control of luminescence.

The chemical introduction of a photoswitchable ligand into ion channel structures should make it possible to study the diverse roles of neurotransmitters and receptors in the brain.

The action of ultrasound on mechanically responsive functional groups — so-called mechanophores — embedded in a polymer chain often permits unusual chemical transformations. There is now a systematic effort to quantify the reactivity of mechanophores in relation to their structure.

Two separate studies show how DNA tiles can be used in automated assembly processes: one system self-replicates, the second assembles the output of a molecular computation.

A reversible covalent reaction in which two oxygen-insensitive radicals combine to form a carbon–carbon bond provides the mechanism by which a polymer gel can self-heal at room temperature without the need for any external stimulus.

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.

Drug-likeness is a key consideration when selecting compounds during the early stages of drug discovery, but its evaluation in absolute terms does not adequately reflect the spectrum of compound quality. Here, an intuitive and transparent quantitative measure of drug-likeness is proposed that attempts to capture the abstract notion of aesthetics in medicinal chemistry.

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.

Light-sensitive ligands can be used to regulate neurobiological receptors with high spatiotemporal precision. Here, the optochemical control of neuronal nicotinic acetylcholine receptors, using both photoswitchable tethered agonists and antagonists, is described. These rationally designed hybrid photoreceptors will facilitate the investigation of the physiological and pathological functions of nicotinic receptors in the brain.

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.

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.

A 16-member diastereoisomer library known to contain macrosphelides A and E is synthesized as a mixture with the aid of a new encoding strategy for fluorous mixture synthesis. A simple process of sequential demixing and tag removal provides each of the isomers in individual, pure form. Analysis of the other library members ultimately leads to a structural reassignment for macrosphelide D.

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.

Mixed-metal oxide catalysts oxidize hydrocarbons into CO and CO₂ through surface oxygen species that have yet to form lattice oxide ions. The one-step oxidation of decane into a range of oxygenated aromatics by a fully oxidized iron molybdate catalyst has now revealed that these species can also be involved in selective oxygen insertion.

Owing to peculiar properties, helium has taken both the main and supporting roles in scientific discoveries over the years. Christine Herman explores just what makes it such a cool element.