Highly dynamic motion of crown ethers along oligolysine peptide chains

Abstract

Molecular mobility has attracted considerable attention in supramolecular chemistry and biochemistry, but the simple question of whether a small molecule can move directly between different binding sites of a multitopic host without intermediate dissociation has not been addressed so far. To study such processes, we consider hydrogen/deuterium exchange experiments on a model system comprising complexes formed between 18-crown-6 and oligolysine peptides. Because direct binding-site hopping is indistinguishable in solution from a dissociation/reassociation mechanism, here we show that the high vacuum of a mass spectrometer offers a unique environment for probing such processes. The highly dynamic motion of crown ethers along oligolysine peptide chains proceeds mechanistically by a simultaneous transfer of the crown ether from its ammonium ion binding site to a nearby amino group together with a proton. Furthermore, the exchange experiments unambiguously reveal the zwitterionic structure of the 18-crown-6/oligolysine complexes, highlighting the versatility and potential of gas-phase experiments for investigating non-covalent interactions.

Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

“…9, 10, 11 The engineering of such systems has been achieved principally through the design of molecular recognition partners, thereby fine tuning the molecular recognition event to meet the demands of specific applications. A number of synthetic receptors including cucurbit[n]uril (CB[n]),9, 12 cyclodextrins,13, 14 cyclophanes,15 calixarenes,16 and crown ethers17,18 have been used for this purpose. Of these host systems, the cucurbit[n]uril (CB[n]) family of macrocyclic receptors is particularly useful due to their well defined structure and recognition properties coupled with their ability to form stable host-guest inclusion complexes with a wide variety of guest molecules in aqueous media 19, 20, 21.…”

Multivalency in the Gas Phase: H/D Exchange Reactions Unravel the Dynamic “Rock ’n’ Roll” Motion in Dendrimer–Dendrimer Complexes

“…If, however, other functional groups can contribute by stabilizing intermediates, so‐called relay mechanisms12, 13 can help circumvent problems related to larger proton affinity differences. This is certainly the case in crown ether–dendrimer complexes 7a. In such cases, the proton affinity differences are usually less important and a broader range of exchange reagents can therefore be used.…”

Supramolecular reactivity in the gas phase: investigating the intrinsic properties of non-covalent complexes

“…The conceptual idea to study the intracomplex dynamics in the crown-peptide complexes is based on this protective group behaviour: 36 if the crown ethers are stationary and cannot leave their positions, the corresponding ammonium protons remain protected and only those groups that are not complexed to a crown ether will undergo the HDX. If the crown is mobile, all protons should be exchangeable.…”