Henrik D. F. Winkler

Integrative self-sorting: construction of a cascade-stoppered hetero[3]rotaxane.

In this Communication, a competing self-sorting system containing benzo-21-crown-7, dibenzo-24-crown-8 and two secondary ammonium salts is constructed, which is then modified to achieve a hetero[3]pseudorotaxane with a specific sequence of wheels. With these two systems, we successfully demonstrate the concept of integrative self-sorting, and their relation. Furthermore, based on this self-sorting scheme, a hetero[3]rotaxane with an efficient stopper cascade has been synthesized.

Highly dynamic motion of crown ethers along oligolysine peptide chains

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.

Dynamic Motion in Crown Ether Dendrimer Complexes: A “Spacewalk” on the Molecular Scale

Brownian motion, the rotation of molecules, and vibrations within molecules are typical forms of thermal motion. Fast chemical equilibria, such as the inversion at the ammonia nitrogen atom, the interconversion of conformers in alkanes, or highly dynamic association/dissociation processes in weakly bound noncovalent complexes are also thermally induced. In the context of noncovalent complexes, it is fascinating to examine whether an intracomplex migration of a guest molecule between different binding sites of a multitopic host is possible and how a motion like this could be monitored. Herein, the first five generations (G1–G5) of polyamino propylene amine (POPAM) dendrimers serve as prototypical multitopic hosts. We address the question, whether crown ethers can directly move from binding site to binding site on the dendrimers periphery without intermediate dissociation/reassociation (Figure 1). Furthermore, if this molecular “spacewalk” is indeed possible, it raises the question as to by what mechanism it proceeds. In solution, the detection of such an intracomplex binding-site hopping is challenging if not impossible, because it is always superimposed by dissociation/reassociation equilibria. Therefore, it is necessary to isolate the complexes from each other and from the corresponding free building blocks to suppress any intercomplex guest-exchange reactions. The high vacuum inside a mass spectrometer is ideally suited to achieve the isolation of the complexes as the complexes there are like-charged and thus efficiently separated from each other by charge repulsion. Also, reactions with neutral crown ether molecules can be excluded. Fragmentation of the crown ether/dendrimer complexes would be the only source for the appearance of neutral crown ethers in the gas phase. Therefore, their partial pressure is much too low to result in an efficient reattachment during the short time they spend inside the instrument before being pumped away. However, this approach comes with the difficulty that any intramolecular process does not change the complex ion s molecular mass and thus remains undetectable by a simple determination of the mass-to-charge ratio (m/z). Therefore, a gas-phase reaction is required that probes the guest s motion. Such a reaction must a) proceed energetically below the complex dissociation energy, b) cause a mass shift, and c) be directly linked to the guest movement. To realize this idea, we chose POPAM dendrimers as the multitopic scaffold. These dendrimers have highly branched onion-layer-type structures (Figure 1). From each generation (Gn) to the next, the number of peripheral amino groups doubles from four in theG1 dendrimer to 64 inG5. Their gasphase chemistry has been studied in detail. In the absence of a solvating agent, protonation is likely to occur at interior tertiary amines rather than the peripheral primary NH2 groups. To examine the host–guest chemistry of dendritic molecules in the gas phase is generally a challenging and byand-large unexplored field of research. Only a few examples exist to date. In our study, [18]crown-6 serves as the guest, it binds to primary ammonium ions in solution, and in the gas phase. Dendritic crown ether/ammonium complexes are Figure 1. Chemical structure of [18]crown-6 and a fourth generation (G4) POPAM dendrimer. Starting with a 1,4-diaminobutane core, the nth shell of branches is divergently grown on the (n 1)th generation dendrimer by two Michael additions of acrylnitrile to each branch and subsequent hydrogenolytic reduction of the nitrile groups. The red arrows symbolize the main question of the present study: Can crown ethers move freely along the periphery of POPAM dendrimers without intermediate dissociation of the complex? As this process proceeds in the high vacuum inside a mass spectrometer, we refer to it as a molecular “spacewalk”.

Gas-phase organocatalysis with crown ethers

Catalytic cycles can be investigated in detail in the gas phase in a step-by-step manner by tandem mass spectrometric experiments that allow for the mass-selection of each of the intermediates prior to the subsequent step. In the present article, we describe large crown ethers (dibenzo-24-crown-8 to dibenzo-30-crown-10) to mediate the E2-elimination of propene from crown ether-propylammonium complexes giving rise to NH4+/crown ether complexes. A back exchange of the ammonia against propyl amine completes the catalytic cycle. To the best of our knowledge, this reaction cycle represents the first example of organocatalysis in the gas-phase. In addition, the larger crown ethers significantly accelerate the H/D-exchange reaction of the five NH hydrogen atoms in singly protonated ethylenediamine as compared to the analogous smaller crown ether complexes. This effect, which is not observed for the propylammonium complexes, can be rationalized by a favorable pre-organization of the protonated ethylenediamine ion within the cavity of the crown ether through hydrogen bonding to both the ammonium and the amine groups. Within this complex, the H/D-exchange can proceed through an efficient “relay” mechanism. A comparison of the H/D-exchange behavior of ammonium complexes with differently sized crown ethers reveals a distinct reactivity pattern that strongly depends on the crown ether size. While 18-crown-6 acts as a non-covalent protective group suppressing the H/D-exchange almost completely, smaller and larger crown ethers exhibit higher exchange rates.

Gas-phase H/D-exchange experiments in supramolecular chemistry

This review discusses the potential of gas-phase H/D-exchange (HDX) reactions for supramolecular chemistry. The exchange of labile H against D atoms can help unravel structural details of supramolecules—in particular when combined with other gas-phase experiments, e.g. ion-mobility MS. The presence of different, non-interconverting structures in an ion population can lead to bimodal exchange distributions. Since hydrogen bonding has an effect on the exchange rates, the number and positions of hydrogen bonds can often be determined. Zwitterionic and charge-solvated structures of amino acids and peptides can be distinguished. Beyond structure, dynamic features such as the mobility of building blocks within complexes can be investigated.

Encapsulation of Luminescent Homoleptic [Ru(dpp)3]2+‐Type Chromophores within an Amphiphilic Dendritic Environment

A new series of homoleptic metallodendrimers has been synthesized through ruthenium-metal complexation by dendritically modified bathophenanthroline ligands. The presence of hydrophilic oligo(ethylene glycol) groups on the surface of the monodisperse metal complexes enabled the solubilization of all of the fractal species in a wide range of solvents, including water. The specific properties of all of these compounds have been systematically investigated by using photophysical techniques as a function of the generation number. Accordingly, the encapsulation of the highly luminescent [Ru(dpp)(3)](2+)-type (dpp=4,7-diphenyl-1,10-phenanthroline) core unit within a dendritic microenvironment creates a powerful means to shield the center from dioxygen quenching. This shielding effect, as exerted on the phosphorescent ruthenium-derived center, is reflected by enhanced emission intensities and extended excited-state lifetimes that are close to the highest values reported so far, even in an air-equilibrated aqueous medium. Interestingly, when inspecting the largest dendritic assembly, that is, the third-generation assembly, significant drops in emission quantum yields and lifetimes are observed. This anomalous behavior has been attributed to the folding of the branches towards the luminescent core.