Although many enzymes can promote chemical reactions by tuning substrate properties purely through the electrostatic environment of a docking cavity, this strategy has proven challenging to mimic in synthetic host-guest systems. Here, we report a highly charged, water-soluble, metal-ligand assembly with a hydrophobic interior cavity that thermodynamically stabilizes protonated substrates and consequently catalyzes the normally acidic hydrolysis of orthoformates in basic solution, with rate accelerations of up to 890-fold. The catalysis reaction obeys Michaelis-Menten kinetics and exhibits competitive inhibition, and the substrate scope displays size selectivity, consistent with the constrained binding environment of the molecular host.

Synthetic chemists have provided a wide array of supramolecular assemblies able to encapsulate guest molecules. The scope of this tutorial review focuses on supramolecular host molecules capable of reversibly encapsulating polyatomic guests. Much work has been done to determine the mechanism of guest encapsulation and guest release. This review covers common methods of monitoring and characterizing guest exchange such as NMR, UV-VIS, mass spectrometry, electrochemistry, and calorimetry and also presents representative examples of guest exchange mechanisms. The guest exchange mechanisms of hemicarcerands, cucurbiturils, hydrogen-bonded assemblies, and metal–ligand assemblies are discussed. Special attention is given to systems which exhibit constrictive binding, a motif common in supramolecular guest exchange systems.

From Yeast to Therapeutic?: Yeast has shown some promise as a model system to generate lead compounds that could have therapeutic potential for the cellular problems associated with neurodegenerative diseases. Along these lines, Tardiff et al. (p. 979 , published online 24 October) and Chung et al. (p. 983 , published online 24 October) describe the results of multiple screens in yeast that lead to the identification of a potential therapeutic compound to combat the cytotoxic affect of α-synuclein accumulation. The compound was able to reverse the pathological hallmarks of Parkinson's disease in cultured neurons derived from patients with α-synuclein–induced Parkinson's disease dementia.

Hydrogen sulfide (H₂S) is an important biological messenger but few biologically-compatible methods are available for its detection. Here we report two bright fluorescent probes that are selective for H₂S over cysteine, glutathione and other reactive sulfur, nitrogen, and oxygen species. Both probes are demonstrated to detect H₂S in live cells.

Current methods for modulating and measuring biological H₂S, as well as practical considerations for working with H₂S are provided.