Analytical chemistry: a dendritic signal amplifier.

deuterating reagent ultimately becomes detached from the complex, with the net effect of one hydrogen atom being replaced with a deuterium atom. This H/D exchange process may repeat multiple times in the gas phase. Other pathways that are independent of the charge site and involve the interaction of the deuterating reagent directly with the labile hydrogen atom are typically higher in energy and result in slow or no H/D exchange. Within a non-covalent complex containing protonated amine groups, one might anticipate that a crown ether could remain permanently associated with one specific protonated amine group, thus blocking the possibility of H/D exchange at that site. However, complexes such as [(18C6)7·Lys15+7H], in which each of the seven protonated amines is coordinated by a crown ether molecule, still undergo virtually complete H/D exchange. Schalley’s innovative strategy provides compelling evidence that the extensive exchange of all labile hydrogens for deuteriums within the peptide/crown ether complexes is facilitated by extensive shuttling of the mobile crown ethers. In this way, all amine groups — even those initially coordinated by crown ether molecules — become available for H/D exchange (Fig. 1). Such a process entails synchronous disruption and formation of multiple hydrogen bonds with net survival of the original non-covalent complexes despite the significant re-positioning of the crown ethers. Each 18C6 molecule migrates with an associated proton between amine groups and does not remain permanently fixed at its initial ammonium binding site or move as a neutral molecule between ammonium sites. Furthermore, comparative experiments using a conventional acid-terminated peptide and an amide-terminated peptide prove that, when possible, the peptide adopts a zwitterionic form — in which a proton has transferred from the C-terminal carboxylic acid to one of the amino groups — affording an additional protonated amine group, which is essential for the relay mechanism. The impressive ability of H/D exchange reactions to yield insight into structures of gas-phase ions and aid in unravelling the dynamic behaviour of supramolecular assemblies is showcased in elegant fashion by Schalley’s team. The implications of these findings are far-reaching. There are opportunities for significant molecular mobility within non-covalent complexes — as illustrated by the migration of crown ether molecules along a peptide — and this example establishes a precedent for potentially more elaborate movement in other types of supramolecular assemblies. Mapping this type of dynamic behaviour in biologically relevant complexes remains an intriguing challenge for the future and could lead to new insight into the mechanisms of biological function. ❐