Chalcogen Bond Mediated Enhancement of Cooperative Ion-Pair Recognition

A series of heteroditopic receptors containing halogen bond (XB) and unprecedented chalcogen bond (ChB) donors integrated into a 3,5-bis-triazole pyridine structure covalently linked to benzo-15-crown-5 ether motifs exhibit remarkable cooperative recognition of halide anions. Multi-nuclear ¹H, ¹³C, ¹²⁵Te and ¹⁹F NMR, ion pair binding investigations reveal sodium cation–benzo-crown ether binding dramatically enhances the recognition of bromide and iodide halide anions, with the chalcogen bonding heteroditopic receptor notably displaying the largest enhancement of halide binding strength of over two hundred-fold, in comparison to the halogen bonding and hydrogen bonding heteroditopic receptor analogues. DFT calculations suggest crown ether sodium cation complexation induces a polarisation of the sigma hole of ChB and XB heteroditopic receptor donors as a significant contribution to the origin of the unique cooperativity exhibited by these systems.     

Guest-Selective Recognition in a Flexible Bipyridinium-Based Framework in a Reversible Crystal-to-Crystal Fashion

A flexible bipyridinium-linker-based porous host framework with electron-accepting pore surface, namely, [Zn₂( L )(pmc)_1.5] ⋅ 12 H₂O ( 1 ; L⋅ Cl₂=1,1′-[1,4-phenylene-bis(methylene)]bis(4,4′-bipyridinium) dichloride, H₄pmc=pyromellitic acid) exhibits recognition of phenol and aromatic amine guests based on adsorbent–adsorbate charge-transfer interactions. Significantly, the resultant guest-encapsulated complexes 1@Guests can all be characterized by single-crystal X-ray diffraction. The host framework undergoes a reversible single crystal-to-single crystal transformation in response to the inclusion of different guests with flexible torsional motions of the hexagonal ring and the trapezoid-shaped bipyridinium groups. Such recognition can be visibly monitored and detected by obvious color changes. The host framework could also be recovered, and this suggested that guest sorption/desorption is reversible and that the host framework could be reused in potential applications. This work may provide an effective way to develop porous materials with special emphasis on applications involving guest recognition.     

Computational NMR Spectra of o-Benzyne and Stable Guests and Their Hemicarceplexes

The incarceration of o-benzyne and 27 other guest molecules within hemicarcerand 1 , as reported experimentally by Warmuth, and Cram and co-workers, has been studied by density functional theory (DFT). The ¹H NMR chemical shifts, rotational mobility, and conformational preference of the guests within the supramolecular cage were determined, which showed intriguing correlations of the chemical shifts with structural parameters of the host–guest system. Furthermore, based on the computed chemical shifts reassignments of some NMR signals are proposed. This affects, in particular, the putative characterization of the volatile benzyne molecule inside a hemicarcerand, for which our CCSD(T) and KT2 results indicate that the experimentally observed signals are most likely not resulting from an isolated o-benzyne within the supramolecular host. Instead, it is shown that the guest reacted with an aromatic ring of the host, and this adduct is responsible for the experimentally observed signals.     

Binding propensity and selectivity of cationic,anionic, and neutral guests with model hydrophobic hosts: A first principles study

Computations play a critical role in deciphering the nature of host–guest interactions both at qualitative and quantitative levels. Reliable quantum chemical computations were employed to assess the nature, binding strength, and selectivity of ionic, and neutral guests with benzenoid hosts. Optimized complex structures reveal that alkali and ammonium ions are found to be in the hydrophobic cavity, while halide ions are outside, while both complexes elicit substantial binding energy. The origin of the selectivity of host toward the guest has been traced to the interaction and deformation energies, and the nature of associated interactions is quantified using energy decomposition and the Quantum Theory of Atoms in Molecules analyses. While the larger hosts lead to loosely bound complexes, as assessed by the longer intermolecular distances, the binding strengths are proportional to the size of the host systems. The binding of cationic complexes is electrostatic or polarization driven while exchange term dominates the anionic complexes. In contrast, dispersion contribution is a key in neutral complexes and plays a pivotal role in stabilizing the polyatomic complexes.     

Redox-Guest-Induced Multimode Photoluminescence Switch for Sequential Logic Gates in a Photoactive Coordination Cage

Molecular or supramolecular level photoluminescence (PL) modulation combining chemical and photonic input/output signals together in an integrated system can provide potential high-density data memorizing and process functions intended for miniaturized devices and machines. Herein, a PL-responsive supramolecular coordination cage has been demonstrated for complex interactions with redox-active guests. PL signals of the cage can be switched and modulated by adding or retracting Fc derivatives or converting TTF into different oxidation states through chemical or photochemical pathways. As a result, reversible or stepwise PL responses are displayed by these host–guest systems because of the occurrence of photoinduced electron-transfer (PET) or fluorescence resonance energy transfer (FREnT) processes, providing unique nanodevice models bearing off/on logic gates or memristor-like sequential memory and Boolean operation functions.     

Modeling the Reaction of Carboxylic Acids and Isonitriles in a Self-Assembled Capsule

Quantum chemical calculations were used to study the reaction of carboxylic acids with isonitriles inside a resorcinarene-based self-assembled capsule. Experimentally, it has been shown that the reactions between p-tolylacetic acid and n-butyl isonitrile or isopropyl isonitrile behave differently in the presence of the capsule compared both with each other and also with their solution counterparts. Herein, the reasons for these divergent behaviors are addressed by comparing the detailed energy profiles for the reactions of the two isonitriles inside and outside the capsule. An energy decomposition analysis was conducted to quantify the different factors affecting the reactivity. The calculations reproduce the experimental findings very well. Thus, encapsulation leads to lowering of the energy barrier for the first step of the reaction, the concerted α-addition and proton transfer, which in solution is rate-determining, and this explains the rate acceleration observed in the presence of the capsule. The barrier for the final step of the reaction, the 1,3 O→N acyl transfer, is calculated to be higher with the isopropyl substituent inside the capsule compared with n-butyl. With the isopropyl substituent, the transition state and the product of this step are significantly shorter than the preceding intermediate, and this results in energetically unfavorable empty spaces inside the capsule, which cause a higher barrier. With the n-butyl substituent, on the other hand, the carbon chain can untwine and hence uphold an appropriate guest length.     

Saccharide Recognition by a Three-Arm-Shaped Host Having Preorganized Three-Dimensional Hydrogen-Bonding Sites

Generally, cage-shaped hosts for saccharides can bind strongly to guest molecules because of the three-dimensional preorganized hydrogen-bonding sites. However, the preparation of cage molecules is often difficult because of the low yield of the macrocyclization step. Here, we report a three-arm-shaped molecule possessing pyridine-acetylene-phenol units as a new kind of host having a preorganized three-dimensional hydrogen-bonding site. This three-arm-shaped host was readily prepared compared to a cage-shaped analogue. This host associated with lipophilic glycosides to form chiral complexes, and the association constants were sufficiently high as to be comparable to those of the cage-shaped analogue. Furthermore, this host extracted native monosaccharides into a lipophilic solvent.     

How important is the dispersion interaction for cyclobis(paraquat‐p‐phenylene)‐based molecular “shuttles”? A theoretical study

Inclusion complexes of cyclobis(paraquat‐p‐phenylene) and various aromatic molecules in their neutral and oxidized form were studied at the LMP2/6‐311+G**//BHandHLYP/6‐31G* level of theory, which represents the highest level theoretical study to date for these complexes. The results show that it is dispersion interaction that contributes most to the binding energy. One electron oxidation of a guest molecule leads to complete dissociation of inclusion complex generating strong repulsion potential between guest and host molecules. Electrostatic interactions also can play an important role, provided the guest molecule has a dipole moment; however, dispersion interactions always dominate in binding energy. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Concentration-Dependent Self-Assembly of an Unusually Large Hexameric Hydrogen-Bonded Molecular Cage

The sizes of available self-assembled hydrogen-bond-based supramolecular capsules and cages are rather limited. The largest systems have volumes of approximately 1400–2300 ų. Herein, we report a large, hexameric cage based on intermolecular amide–amide dimerization. The unusual structure with openings, reminiscent of covalently linked cages, is held together by 24 hydrogen bonds. With a diameter of 2.3 nm and a cavity volume of ∼2800 ų, the assembly is larger than any previously known capsule/cage structure relying exclusively on hydrogen bonds. The self-assembly process in chlorinated, organic solvents was found to be strongly concentration dependent, with the monomeric form prevailing at low concentrations. Additionally, the formation of host–guest complexes with fullerenes (C₆₀ and C₇₀) was observed.     

Guest Recognition Control Accompanied by Stepwise Gate Closing and Opening of a Macrocyclic Metallohost

Host–guest binding behavior of macrocyclic hosts is significantly influenced by the shapes and sizes of the hosts. In particular, closing/opening the apertures of the hosts controls the guest uptake/release. A post-metalation modification method was used to achieve the open/close conversions. The starting open complex, [LCo₂(pip)₄](OTf)₂, was efficiently converted to the closed complex, [LCo₂(hda)₂](OTf)₂, which has a doubly bridged structure. The conversion of this closed complex to the open complex [LCo₂(hda)₂(OAc)]⁺ was too slow to be completed, but this gate-opening was dramatically accelerated by the addition of Na⁺. The Na⁺ binding was also significantly enhanced by the gate-opening, that is, conversion of [LCo₂(hda)₂]²⁺ to [LCo₂(hda)₂(OAc)]⁺.     

Amphoteric Homotropic Allosteric Association between a Hexakis-Urea Receptor and Dihydrogen Phosphate

Conformationally flexible hexakis-urea 1 was synthesized efficiently by condensing hexakis(aminomethyl)benzene with 4-nitrophenyl-(3,5-di-tert-butylphenyl)carbamate. The hexakis-urea 1 is unexpectedly soluble in organic solvents of low polarity due to intramolecular hydrogen bonding. The hexakis-urea 1 recognizes chloride, bromide, and acetate in a 1:2 host-guest ratio and in a positive allosteric manner in CDCl₃. The ability of 1 to recognize dihydrogen phosphate is a unique outcome, and the structure of the associated complex, which contains four dihydrogen phosphate ions, was clarified by single-crystal X-ray structural analysis. However, in solution, a complex with three dihydrogen phosphate ions was identified. The dihydrogen phosphate association in CDCl₃ proceeds in an amphoteric allosteric manner; in a positive allosteric manner (K₁<K₂) in the first step and a negative allosteric manner (K₂>K₃) in the subsequent step.     

Supramolecular Metallacycles and Their Binding of Fullerenes

The synthesis of a new triaminoguanidinium-based ligand with three tris-chelating [NNO]-binding pockets and C₃ symmetry is described. The reaction of tris-(2-pyridinylene-N-oxide)triaminoguanidinium salts with zinc(II) formate leads to the formation of cyclic supramolecular coordination compounds which in solution bind fullerenes in their spherical cavities. The rapid encapsulation of C₆₀ can be observed by NMR spectroscopy and single-crystal X-ray diffraction and is verified using computation.     

Helical,Axial, and Central Chirality Combined in a Single Cage: Synthesis,Absolute Configuration,and Recognition Properties

The synthesis of eight enantiopure molecular cages (four diastereomeric pairs of enantiomers) comprising a helically chiral cyclotriveratrylene (CTV) unit, three axially chiral binaphthol linkages, and three centrally asymmetric carbon atoms of a trialkanolamine core, is described. These new cages constitute a novel family of hemicryptophanes, which combine three classes of chirality. Their absolute configuration was successfully assigned by a chemical correlation method to overcome the signals overlap in the ECD spectra of the binaphtol and CTV units. Stereoselective recognition of glucose and mannose derivatives was investigated with these new chiral cages. Excellent enantio‐ and diastereoselectivity were reached, since in some cases, both exclusive enantio‐ and diastereo‐discrimination have been observed. In addition, compared with the most relevant hemicryptophanes, these new cages also exhibit improved binding affinities.     

A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and Dimeric Adapter Protein 14-3-3

Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation-dependent mono- or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)-based supramolecular system, which in conjunction with the 14-3-3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine–glycine–glycine (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8-induced dimerization of the ERα epitope augmented its affinity towards 14-3-3 through a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex revealed molecular insight into the multiple supramolecular interactions between the protein, the peptide, and Q8.     

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

The allosteric control of the receptor properties of two flexible covalent cages is reported. These receptors consist of two zinc(II) porphyrins connected by four linkers of two different sizes, each incorporating two 1,2,3-triazolyl ligands. Silver(I) ions act as effectors, responsible for an on/off encapsulation mechanism of neutral guest molecules. Binding silver(I) ions to the triazoles opens the cages and triggers the coordination of pyrazine or the encapsulation of N,N′-dibutyl-1,4,5,8-naphthalene diimide. The X-ray structure of the silver(I)-complexed receptor with short connectors is reported, revealing the hollow structure with a cavity well-defined by two eclipsed porphyrins. Rather unexpectedly, the crystallographic structure of this receptor with pyrazine as a guest molecule showed that the cavity is occupied by two pyrazines, each binding to the zinc(II) porphyrin in a monotopic fashion.     

Chiral Recognition of Amino Acid Esters in Organic Solvents Using a Glucose-Based Receptor

Due to the chemical and biological relevance of amino acids, efficient methods for the recognition and separation of their enantiomers are highly sought after. Chiral receptors based on extended molecular scaffolds are typically employed for this purpose. These receptors are often effective only in specific environments and towards a narrow scope of amino acid guests. Recently we reported a simple, glucose-based macrocycle capable of enantioselective binding of a broad range of amino acid methyl esters in water. Herein we demonstrate that the same receptor can be used for chiral recognition of amino acid esters in organic solvents. We show that the binding affinity and selectivity of the receptor are highly dependent on the coordinating strength of the solvent. An in-depth analysis of the receptor’s conformation and its interactions with amino acid methyl esters allowed us to propose a binding mode of amino acids to the receptor in CDCl₃. The binding modes in CDCl₃ and D₂O were then compared, highlighting the main interactions responsible for binding affinity and selectivity in each solvent. We envision that the insight provided by this study will facilitate the development of further amino acid receptors based on monosaccharides with improved binding affinities and both enantio- as well as chemoselectivities.     

A Regulable Internal Cavity inside a Resorcinarene-Based Hemicarcerand

Covalent organic capsules, such as carcerands and hemicarcerands, are an interesting class of molecular hosts. These container molecules have confined spaces capable of hosting small molecules, although the fact that the size of the inner cavities cannot be changed substantially limits the scope of their applications. The title covalently linked container was produced by metal-directed dimerization of a resorcinarene-based cavitand having four 2,2′-bipyridyl arms on the wide rim followed by olefin metathesis at the vertices of the resulting capsule with a second-generation Grubbs catalyst. The covalently linked bipyridyl arms permit expansion of the inner cavity by demetalation. This structural change influences the molecular recognition properties; the metal-coordinated capsule recognizes only 4,4′-diacetoxybiphenyl, whereas the metal-free counterpart can encapsulate not only 4,4′-diacetoxybiphenyl, but also 2,5-disubstituted-1,4-bis(4-acetoxyphenylethynyl)benzene, which is 9.4 Å longer than the former guest. Molecular mechanics calculations predict that the capsule expands the internal cavity to encapsulate the long guest by unfolding the folded conformation of the alkyl chains, which demonstrates the flexible and regulable nature of the cavity. Guest competition experiments show that the preferred guest can be switched by metalation and demetalation. This external-stimuli-responsive guest exchange can be utilized for the development of functional supramolecular systems controlling the uptake, transport, and release of chemicals.     

Shielded alkyl-functionalised rotaxane host cavities for improved anion recognition

The synthesis and anion recognition properties of four novel [2]rotaxane host architectures containing additional alkyl functionality integrated within macrocyclic and axle components to shield the binding cavity from the solvent are described. The rotaxane species containing a tetra(methyl)-functionalised macrocycle component is found to be a weaker anion complexant than the equivalent unfunctionalised receptor, which is likely due to steric hindrance restricting the anion's access to the interlocked cavity. Rotaxane molecules containing tetra(methyl)-functionalised axle components are also investigated, and the additional alkyl functionality serves to enhance anion binding affinity and selectivity when incorporated within the axle's flexible ethylene linkages. Moreover, the equivalent unfunctionalised rotaxane displays a rare preference for oxoanions over chloride guest species.     

Dual Responsive Regulation of Host–Guest Complexation in Aqueous Media to Control Partial Release of the Host

The regulation of the concentration of a wide range of small molecules is ubiquitous in biological systems because it enables them to adapt to the continuous changes in the environmental conditions. Herein, we report an aqueous synthetic system that provides an orchestrated, temperature and pH controlled regulation of the complexation between the cyclobis(paraquat-p-phenylene) host ( BBox ) and a 1,5-dialkyloxynaphthalene ( DNP ) guest attached to a well-defined dual responsive copolymer composed of N-isopropylacrylamide as thermoresponsive monomer and acrylic acid as pH-responsive monomer. Controlled, partial release of the BBox , enabling control over its concentration, is based on the tunable partial collapse of the copolymer. This colored supramolecular assembly is one of the first synthetic systems providing control over the concentration of a small molecule, providing great potential as both T and pH chromic materials and as a basis to develop more complex systems with molecular communication.