Selective Stabilization of Self-Assembled Hydrogen-Bonded Molecular Capsules Through π–π Interactions

Subtle noncovalent forces such as π–π interactions play an import role in the folding of biological macromolecules such as DNA and proteins. We describe here a system where such interactions on the outside of a molecular capsule trigger a selective change of its structure as a self-assembled receptor

Guest-Induced, Selective Formation of Isomeric Capsules with Imperfect Walls

The majority of building blocks in self-assembled capsules feature high symmetry. Reducing this symmetry inevitably leads to expanded possibilities for isomerism. Here, we report a deep cavitand host with one short and three long walls. Its dimerization to hydrogen-bonded capsules in the presence of suitable guest molecules can lead to two constitutional isomers. A given guest induces the predominant formation of only one isomer. The unexpected selectivity is interpreted in terms of the different hydrogen-bonding patterns of the capsules and their effects on the size, shape, and dynamics of the capsules’ spaces

Cavitands as Chaperones for Monofunctional and Ring-Forming Reactions in Water

Cyclic processes involving medium-sized rings show low rates because internal strainstorsions and transannular interactionsare created during the reactions. High dilution is often used to slow the competing bi- and higher-molecular processes but cannot accelerate the desired cyclization reaction. Here we apply cavitands to the formation of medium- to large-sized rings through conversion of long-chain diisocyanates to cyclic ureas. The reactions take place in aqueous (D₂O) solution, where hydrophobic forces drive the starting materials into the cavitands in folded conformations. The guest assumes the shape to fill the space properly, which brings the reacting ends closer together than they are in bulk solvent. Complexation overcomes some of the internal strains involved in precyclization shapes of the guest molecules and accelerates the cyclization. The results augur well for applications of water-soluble cavitands to related processes such as remote functionalization reactions

Encapsulation of Ion Pairs in Extended, Self-Assembled Structures

Encapsulation of ion pairs in small spaces that are isolated from the medium is expected to result in amplified interactions between the ions. Yet, sequestration of ion pairs in self-assembled capsules is complicated by competition of the acids and bases for binding directly to the assembly components. We describe here a hydrogen-bonded capsule <b>1.2</b>_<b>8</b><b>.1</b> that accommodates two γ-picolines and two acids as ion pairs. The supramolecular structure of the discrete 14-component assembly is characterized by NMR spectroscopy. The structure reveals the acids in the tapered ends of the capsule and γ-picoliniums near the glycoluril spacers in the capsule’s center. Similar acid–base ion pairs are also obtained with 4-ethylpyridine, γ-picoline with difluoroacetic acid, and γ-picoline with trifluoromethanesulfonic acid. The ¹H NMR spectrum of the γ-picoline/trifluoroacetic acid ion pair shows a signal at δ = 18.7 ppm, indicating the acidic proton is in contact with both the picoline nitrogen and the trifluoroacetate oxygen. Further details about the unusual structures of ion pairs in small spaces are reported

Alkane Lengths Determine Encapsulation Rates and Equilibria

A cylindrical capsule provides an environment for straight-chain alkanes that can properly fill the space through extended or compressed conformations. The encapsulation rates of a series of alkanes were examined and found to be dependent on guest length: the rates of uptake are C₉ > C₁₀ > C₁₁, while complex stability is in the reverse order, C₁₁ > C₁₀ > C₉. Direct competition experiments, pairwise or between all 3 alkanes, maintain this order as the longer alkanes sequentially displace the shorter ones. The distribution of species with time provides a clock for this complex system, which combines elements of self-sorting phenomena and dynamic combinatorial chemistry. The clock can be stopped by replacing the alkanes with the superior guest 4,4′-dimethylazobenzene, then restarted by irradiation

Hydrogen-Bonded Capsules in Water

Hydrogen-bonded capsules constrain molecules into small spaces, where they exhibit behavior that is inaccessible in bulk solution. Water competes with the formation of hydrogen bonds, and other forces for assembly, such as metal/ligand interactions or hydrophobic effects, have been applied. Here we report the reversible assembly of a water-soluble cavitand to a robust capsule host in the presence of suitable hydrophobic guests. The complexes are characterized by conventional NMR methods. Selectivity for guest length and fluorescence quenching of a stilbene guest are used as evidence for hydrogen bonding in the capsule

Synthesis of Fused Indazole Ring Systems and Application to Nigeglanine Hydrobromide

The single-step synthesis of fused tricyclic pyridazino[1,2-<i>a</i>]indazolium ring systems is described. Structural details revealed by crystallography explain the unexpected reactivity. The method is applied to the gram scale synthesis of nigeglanine hydrobromide

Synthesis of Fused Indazole Ring Systems and Application to Nigeglanine Hydrobromide

The single-step synthesis of fused tricyclic pyridazino[1,2-<i>a</i>]indazolium ring systems is described. Structural details revealed by crystallography explain the unexpected reactivity. The method is applied to the gram scale synthesis of nigeglanine hydrobromide

Synthesis of Fused Indazole Ring Systems and Application to Nigeglanine Hydrobromide

The single-step synthesis of fused tricyclic pyridazino[1,2-<i>a</i>]indazolium ring systems is described. Structural details revealed by crystallography explain the unexpected reactivity. The method is applied to the gram scale synthesis of nigeglanine hydrobromide

Quantum Chemical Modeling of Cycloaddition Reaction in a Self-Assembled Capsule

Dispersion-corrected density functional theory is used to study the cycloaddition reaction between phenyl acetylene and phenyl azide inside a synthetic, self-assembled capsule. The capsule is first characterized computationally and a previously unrecognized structure is identified as being the most stable. Next, an examination of the free energies of host–guest complexes is conducted, considering all possible reagent, solvent, and solvent impurity combinations as guests. The experimentally observed relative stabilities of host–guest complexes are quite well reproduced, when the experimental concentrations are taken into account. Experimentally, the presence of the host capsule has been shown to accelerate the cycloaddition reaction and to yield exclusively the 1,4-regioisomer product. Both these observations are reproduced by the calculations. A detailed energy decomposition analysis shows that reduction of the entropic cost of bringing together the reactants along with a geometric destabilization of the reactant supercomplex are the major contributors to the rate acceleration compared to the background reaction. Finally, a sensitivity analysis is conducted to assess the stability of the results with respect to the choice of methodology