Supramolecular Nanosystems


Last updated: August 24, 2017

Selected References

A wide range of projects targets the development of new supramolecular systems with nanoscale dimensions.

In collaboration with the Nanoscale Science Center (NCCR) in Basel, we prepare and study dynamic receptors that function as molecular grippers. These compounds undergo conformational switching between a vase form, capable of complexation of guests in a deep cavity, and a kite form, with a large flat surface. We have shown that this conformational switching can be done both by temperature and pH change and imaged the receptors anchored to gold surfaces at molecular resolution using STM. Furthermore, we demonstrated that Langmuir films of the grippers can be switched from the vase to the kite conformation, a process driven by stoichiometric zinc(II) ion complexation. These systems are now investigated to induce very large molecular motions between two bistable states.

We also prepared the donor-acceptor BODIPY dye-labeled cavitand 1 by a highly convergent, modular route from readily accessible building blocks. Computer modeling, based on X-ray crystal structures of bridged resorcin[4]arene cavitands in both vase and kite conformations suggests a ~1000% difference in the distance between the dye pair in the contracted (~7 Å) and expanded (~7 nm, distance between the two B-atoms) states.

This unprecedentedly large expansion/contraction movement of 1 was clearly proven by both 1H NMR and fluorescence resonance energy transfer (FRET) measurements. Reversible vase-kite switching can be induced by changes in temperature or pH. Upon addition of TFA, the fluorescence of the acceptor dye (λmax = 630 nm) vanishes almost completely, whereas the emission of the donor dye (λmax = 542 nm) doubles in intensity. In the expanded kite state, with a spatial separation of donor and acceptor of ~7 nm, the FRET efficiency is dramatically reduced.

Reversible switching between a closed conformation and an open form is the key property of novel container molecules, a molecular basket and a molecular tube. In the closed form, they encapsulate cycloalkanes such as cyclohexane whereas upon acid-triggered switching to the open form, their binding capabilities are completely turned off. Upon neutralization, the containers return to their closed conformations and guest binding is restored at full strength.


The resorcin[4]arene-based molecular baskets feature well-defined cavities that bind a variety of cycloalkanes and alicyclic heterocycles.  The thermodynamic quantities for inclusion complexation in mesitylene were determined by both 1H NMR spectroscopy and isotheral titration calorimetry (ITC).  A large variation in the association constants Ka was measured for the various 1:1 inclusion complexes: whereas cycloheptane is too large for a good fit inside the container and only binds with 1.7 x 102 M–1, the six-membered morpholine formed a highly stable complex with Ka = 1,7 x 107 M–1.  Both enthalpic and entropic changes favor the inclusion complexation as demonstrated by the ITC data, as illustrated in the Figure below.  In general, complexation is driven by dispersion interactions, C–H...π interactions of the guests with the aromatic walls of the cavity, and optimal cavity filling.  Complexed heterocyclic guest undergo additional polar interactions (C–O...C=O, N–H...π, S...π) with the host.

We also prepared and studied novel redox-active, quinone-based resorcin[4]arene cavitands.  The quinone walls are readily and reversibly reduced to the corresponding hydroquinone moieties and can be readily re-oxidized back in a quantitative fashion.  The actual conformations of both the quinone and hydroquinone-based systems are strongly solvent-dependent and, for the first time, X-ray structures of both the vase and the kite form of a resorcin[4]arene-based cavitand were obtained (see Figure below).  The further development towards reversibly redox-switchable molecular grippers, which in one state exist only in the closed vase form, capable of guest uptake and complexation, and in the other in the open kite form, releasing the guest, is now pursued.

With quinone-based resorcin[4]arene cavitands, we were finally able to create a cavitand whose conformational and binding properties can be reversibly switched in a redox process. Such system holds promise as a molecular gripper for nanomanipulation on surfaces.

We prepared a diquinone-based resorcin[4]arene cavitand that opens to a kite and closes to a vase form upon changing its redox state, thereby releasing and binding guests. The switching mechanism is based on intramolecular H-bonding interactions that stabilize the vase form and are only present in the reduced hydroquinone state. The intramolecular H-bonds were nicely evidenced in the X-ray, IR, and NMR data. In mesitylene-d12, guests such as cyclooctane were bound in the closed, reduced state and fully released in the open, oxidized state. The crystal structure of cyclooctane bound to the cavity of the reduced vase cavitand is shown.

Recently, we were able to prepare the first paramagnetic molecular grippers by generating in a collaborative effort the triplet semiquinone (SQ) states electrochemically, chemically, and photochemically. In these systems, UV/Vis spectroelectrochemistry and EPR spectroscopy were used to evaluate the conformational features of the resorcin[4]arene cavitands. Guest binding properties were found to be enhanced in the SQ state, as compared to the quinone (Q) and hydroquinone (HQ) states. These paramagnetic SQ intermediates open the way to six-state redox switches provided by two conformations (open and closed) in three redox states (Q, SQ, and HQ), possessing distinct binding ability.

Our group has pursued supramolecular porphyrin chemistry since the late 1980s, with the construction of elaborate active models for cytochrome P-450 enzymes and dendritically encapsulated porphyrins to mimic cyctochromes b. We now were able to successfully conclude our efforts started in 1996 to produce authentic models for myoglobin and hemoglobin and, for the first time, provide unambiguous experimental support for the stabilization of the O2-complexes of myoglobin and hemoglobin through a H-bond to the distal imidazole of a His residue.

We prepared an elaborate Co(II) porpyrin model system, featuring both a "proximal" and a "distal" imidazole as well as its O2 complexes. This compound is an excellent model for the natural proteins, which reproduces well some of their crucial properties. Extensive EPR measurements (pulse-EPR methods such as Davies-ENDOR spectroscopy, in collaboration with Prof. Gunnar Jeschke, ETH Zurich) to measure the complete proton hyperfine splittings gave direct evidence for a dipolar H-bonding interaction between the distal N–H and Co(II)-bound O2 in the synthetic complex. A larger hyperfine splitting, indicative of an even stronger H-bond of mainly dipolar nature was observed in the biological system (myoglobin-Co(II)-O2). The insertion of this perfect model into dendrimers to mimic the protein surroundings is now being pursued. Also, we are interested in evaluating the effects of donor/acceptor substitution of the porphyrin and the distal base on the stability of the hydrogen bond to bound dioxygen.

Left: The overlay of the synthetic model with Co.myoglobin modeled into the crystal structure of the protein (adopted from te coverpage of Angew. Chem.). Davies-Endor spectra showed the hyperfine splitting caused by the H-bonding of the "distal" benzimidazole (His imidazole in the protein) to bound O2. Right: Evaluation of the H-bonding geometry in the synthetic O2 complex.

Recently, we showed the diastereoselective assembly of enantiopure alleno-acetylenic ligands, originating from our C-Rich Materials program, upon addition of Zn(II) salts to form triple-stranded helicates which provide a sufficiently large helical cage for the encapsulation of guests.  The electronic circular dichroism (ECD) spectra of the helicates showed strong Cotton effects and excitonic couplings, which were found to be extremely sensitive to the nature of the guest molecules.  This enabled the chemical sensing of nonchromophoric achiral guests of different size based on the induced circular dichroism (ICD) spectra.  As an example, the better binding 1,4-dioxane could be sensed this way in the presence of a larger excess of 1,3-dioxane in the parts-per-million (ppm) concentration range.

Helicate

We also showed that short and longer homochiral strands of alternating alleno-acetylenes and phenanthroline ligands, as well as their corresponding enantiomers, selectively assemble with the addition of silver(I) salt to yield dinuclear and trinuclear double helicates, respectively. Upon increasing the solvent polarity, the dinuclear and trinuclear helicates interlock to form a [2]catenane and an unprecedented bis[2]catenane (see the structure below) bearing 14 chirality elements. Highly selective narcissistic self-sorting was demonstrated for a racemic mixture consisting of both short and long alleno-acetylenic strands.