Hydrogen‐Bond and Metal–Ligand Coordination Bond Hybrid Supramolecular Capsules: Identification of Hemicapsular Intermediate and Dual Control of Guest Exchange Dynamics

Hybrid supramolecular capsules self‐assemble by simultaneously forming hydrogen and metal–ligand coordination bonds on mixing a C₂‐symmetrical cavitand (calix[4]resorcinarene‐based cavitands with ureide and terminal 4‐pyridyl units) with platinum or palladium complexes ([Pt(OTf)₂] or [Pd(OTf)₂] with chelating bisphosphines) in 1:1 ratio. Hemicapsular assemblies formed in the presence of excess amounts of cavitand relative to the platinum or palladium complexes are identified as intermediates in the above self‐assembly process by 2D‐NOESY spectroscopy. External‐anion‐assisted encapsulation of a neutral guest, 4,4′‐diiodobiphenyl, inside the hybrid supramolecular capsules accompanied conformational changes in the hydrogen‐bonding moieties. The in/out exchange ratio of the encapsulated guest depends on the bite angle of the bisphosphine ligand. Addition of DMSO accelerates guest exchange by weakening the hydrogen bonds in the encapsulation complex. Therefore, variations in the structure of the metal complex and amount of polar solvent exert dual control on the dynamics of the guest exchange.     

Recognition of N‐Alkyl and N‐Aryl Acetamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra‐ and intermolecular hydrogen bonds that leads to cavitand‐like structures. Depending on the upper‐rim substituents, self‐inclusion was observed in solution and in the solid state. The self‐inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self‐included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N‐alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C?O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl^?) and ammonium (NH₂⁺) cations of the hosts, and also through CH ??? π interactions between the hosts and guests. The self‐included and host–guest complexes were studied by single‐crystal X‐ray diffraction, NMR titration, and mass spectrometry.     

Ion‐Pair Complexation with a Cavitand Receptor

The capability of resorcinarenes to bind anions within the alkyl feet at the lower rim has been exploited as the starting point for developing a new cavitand able to engulf contact ion pairs of primary ammonium salts in chlorinated solvents with association constants (K_ass) in the range of 10³–10⁴ M ^?1. Methylene bridges were introduced into the upper rim to freeze the resorcinarene in the cone conformation with the four H_down protons converging in the lower pocket, thereby maximizing the CH–anion interactions responsible for the anion binding. Four additional phosphate moieties were introduced into the lower rim in close proximity to the anionic site to provide hydrogen‐bonding‐acceptor P?O groups and promote cation complexation at the bottom of the cavitand. The binding ability of the synthesized ligands was analyzed by ¹H NMR spectroscopy and, when possible, by isothermal titration calorimetry (ITC); the data were in agreement when complementary techniques were used.     

Ferrocene–β‐Cyclodextrin Conjugates: Synthesis,Supramolecular Behavior,and Use as Electrochemical Sensors

Ferrocene with a β‐cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face were conveniently synthesized by regiospecific copper(I)‐catalyzed cycloaddition of 2‐O‐propargyl‐β‐cyclodextrin to azidomethyl or bis(azidomethyl)ferrocene. The supramolecular behavior of the synthesized conjugates in both the absence and presence of bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) was studied by using electrochemical methods (cyclic and differential pulse voltammetry), isothermal titration calorimetry, and NMR spectroscopy (PGSE, CPMG, and 2D‐ROESY). These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates. It was found that the ferrocenyl conjugate with one β‐cyclodextrin unit forms a redox‐controllable head‐to‐head homodimer in aqueous solution. The ferrocene–bis(β‐cyclodextrin) conjugate is present in two distinguishable forms in aqueous solution, each one having a different half‐wave oxidation potential for the oxidation of the ferrocene. By contrast, only one distinguishable form for the oxidized state of the ferrocene–β‐cyclodextrin conjugate is detectable. The redox‐sensing abilities of the synthesized conjugates towards the bile salts were evaluated based on the observed guest‐induced changes in both the half‐wave potential and the current peak intensity of the electroactive moiety.     

Controlling the Host–Guest Interaction Mode through a Redox Stimulus

A proof‐of‐concept related to the redox‐control of the binding/releasing process in a host–guest system is achieved by designing a neutral and robust Pt‐based redox‐active metallacage involving two extended‐tetrathiafulvalene (exTTF) ligands. When neutral, the cage is able to bind a planar polyaromatic guest (coronene). Remarkably, the chemical or electrochemical oxidation of the host–guest complex leads to the reversible expulsion of the guest outside the cavity, which is assigned to a drastic change of the host–guest interaction mode, illustrating the key role of counteranions along the exchange process. The reversible process is supported by various experimental data (¹H NMR spectroscopy, ESI‐FTICR, and spectroelectrochemistry) as well as by in‐depth theoretical calculations performed at the density functional theory (DFT) level.     

Cooperative Binding of Divalent Diamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides, stabilized by an intricate array of hydrogen bonds leading to a cavitand‐like structure, bind amides. The molecular recognition occurs through intermolecular hydrogen bonds between the carbonyl oxygen and the amide hydrogen of the guests and the cation–anion circular hydrogen‐bonded seam of the hosts, as well as through CH ??? π interactions. The N‐alkyl ammonium resorcinarene chlorides cooperatively bind a series of di‐acetamides of varying spacer lengths ranging from three to seven carbons. Titration data fit either a 1:1 or 2:1 binding isotherm depending on the spacer lengths. Considering all the guests possess similar binding motifs, the first binding constants were similar (K₁: 10² M ^?1) for each host. The second binding constant was found to depend on the upper rim substituent of the host and the spacer length of the guests, with the optimum binding observed with the six‐carbon spacer (K₂: 10³ M ^?2). Short spacer lengths increase steric hindrance, whereas longer spacer lengths increase flexibility thus reducing cooperativity. The host with the rigid cyclohexyl upper rim showed stronger binding than the host with flexible benzyl arms. The cooperative binding of these divalent guests was studied in solution through ¹H NMR titration studies and supplemented by diffusion‐ordered spectroscopy (DOSY), X‐ray crystallography, and mass spectrometry.     

Resorcinarene Bis‐Thiacrowns: Prospective Host Molecules for Silver Encapsulation

Mixed‐donor atom tetramethoxy resorcinarene bis‐thiacrown hosts, in which the crown unit contains both hard oxygen and soft sulfur donor atoms, were synthesized for soft metal cation binding. The binding properties were investigated both in solution and in the solid state by NMR spectroscopy and X‐ray crystallography. It was found that the resorcinarene bis‐thiacrowns were able to complex silver cations with remarkable affinity forming readily 1:2 host–guest complexes in solution. The solid state structures also revealed that the bis‐thiacrowns form silver complexes in an unanticipated endo‐ and exo‐cavity fashion within the same host molecule. Both the solution and solid state studies indicated the sulfur atoms to be the major contributing donor atoms in forming the binding interactions with silver cations.     

Complexation between Methyl Viologen (Paraquat) Bis(Hexafluorophosphate) and Dibenzo[24]Crown‐8 Revisited

Paraquat bis(hexafluorophosphate) undergoes stepwise dissociation in acetone. All three species—the neutral molecule, and the mono‐ and dications—are represented significantly under the experimental conditions typically used in host–guest binding studies. Paraquat forms at least four host–guest complexes with dibenzo[24]crown‐8. They are characterized by both 1:1 and 1:2 stoichiometries, and an overall charge of either zero (neutral molecule) or one (monocation). The monocationic 1:1 host–guest complex is the most abundant species under typical (0.5–20 mM ) experimental conditions. The presence of the dicationic 1:1 host–guest complex cannot be excluded on the basis of our experimental data, but neither is it unambiguously confirmed to be present. The two confirmed forms of paraquat that do undergo complexation—the neutral molecule and the monocation—exhibit approximately identical binding affinities toward dibenzo[24]crown‐8. Thus, the relative abundance of neutral, singly, and doubly charged pseudorotaxanes is identical to the relative abundance of neutral, singly, and doubly charged paraquat unbound with respect to the crown ether in acetone. In the specific case of paraquat/dibenzo[24]crown‐8, ion‐pairing does not contribute to host–guest complex formation, as has been suggested previously in the literature.     

[2]Pseudorotaxanes Based on Naphtho‐21‐crown‐7 and Secondary Dialkylammonium Salts: Remarkably Improved Association Constants Among Four Threaded Structures

This research article is focused on the recognition interaction of a new host naphtho‐21‐crown‐7 and four secondary dialkylammonium salts. In acetone, they can form 1:1 host‐guest complexes which belong to slow‐exchange systems. We also found the differences of binding affinity and binding selectivity between the host and its complementary guest moieties, which could be ascribed to the aromatic π‐π stacking effect and the acidity increase of N‐methylene and ammonium hydrogens due to the increasing electron withdrawing ability from butyl to methoxyphenyl to phenyl to p‐cyanophenyl substituents in the recognition motif.     

pH influenced molecular switching with micelle bound cavitands

A series of resorcinarene host-amphiphilic guest complexes have been developed where guest orientation in the host is drastically influenced by pH. Guests appended with a trimethylammonium and a tert-butyl group switch orientation by 180° in response to a buildup of negative charge in the cavitand host.     

Voltammetric Characterization of Redox‐Inactive Guest Binding to LnIII[15‐Metallacrown‐5] Hosts Based on Competition with a Redox Probe

A novel competitive binding assay was implemented to monitor the binding of a redox inactive substrate to a redox inactive metallacrown host based on its competition with ferrocene carboxylate (FcC^?) using cyclic voltammetry (CV). First, the binding of FcC^? to Ln^III[15‐MC‐5] (LnMC) hosts was characterized by cyclic voltammetry. It was shown that the voltammetric half wave potentials, E_1/2, shifted to more positive potentials upon the addition of LnMC. The explicit dependence of E_1/2 with the concentration of LnMC was used to determine the association constants for the complex. The FcC^? binding strength decreased with larger central lanthanide metals in the LnMC hosts, and substantially weaker binding was observed with La^III. X‐ray crystallography revealed that the hydrophobic host cavity incompletely encapsulated FcC^? when the guest was bound to the nine‐coordinate La^III, suggesting the LnMC’s ligand side chains play a substantial role in guest recognition. With knowledge of the MC‐FcC^? solution thermodynamics, the binding affinity of a redox inactive guest was then assessed. Addition of sodium benzoate to a LnMC and FcC^? mixture resulted in E_1/2 shifting back to the value observed for FcC^? in the absence of LnMC. The association constants between benzoate and LnMC’s were calculated via the competitive binding approach. Comparison with literature values suggests this novel assay is a viable method for determining association constants for host–guest systems that exhibit the proper electrochemical behavior. Notably, this CV competitive binding approach does not require the preparation of a modified electrode or a tethered guest, and thus can be generalized to a number of host–guest systems.     

The Redox Coupling Effect in a Photocatalytic RuII‐PdII Cage with TTF Guest as Electron Relay Mediator for Visible‐Light Hydrogen‐Evolving Promotion

A nanocage coupling effect from a redox Ru^II‐Pd^II metal–organic cage (MOC‐16) is demonstrated for efficient photochemical H₂ production by virtue of redox–guest modulation of the photo‐induced electron transfer (PET) process. Through coupling with photoredox cycle of MOC‐16, tetrathiafulvalene (TTF) guests act as electron relay mediator to improve the overall electron transfer efficiency in the host–guest system in a long‐time scale, leading to significant promotion of visible‐light driven H₂ evolution. By contrast, the presence of larger TTF‐derivatives in bulk solution without host–guest interactions results in interference with PET process of MOC‐16, leading to inefficient H₂ evolution. Such interaction provides an example to understand the interplay between the redox‐active nanocage and guest for optimization of redox events and photocatalytic activities in a confined chemical nanoenvironment.     

Rim,Side Arms,and Cavity: Three Sites for the Recognition of Anions by Tetraazolium Resorcinarene Cavitands

Two tetrabenzoimidazolium‐resorcinarene cavitands were prepared and used for the recognition of chloride, bromide, iodide, cyanide, nitrate, perchlorate, hexanoate, benzenesulfonate, and p‐toluenesulfonate. Binding affinities of the two cavitands were determined by ¹H NMR titration and computational analysis. The observed spectral changes were related to specific interaction sites, which were supported by the computational studies. In the case of the C2?H tetrabenzoimidazolium‐resorcinarene, the recognition region of the inorganic anions and hexanoate was located at the rim of the cavitand, although chloride and bromide also interacted with the aromatic C?H bonds located between adjacent arms of the cavitand. By contrast, the recognition of the two anions with an aromatic ring (benzenesulfonate and p‐toluenesulfonate) results from encapsulation of the aromatic part of the anions inside the hydrophobic cavity of the host. In the case of the C2?Me tetrabenzoimizazolium‐resorcinarene receptor, the ability of the molecule to bind all inorganic anions and hexanoate was suppressed, but the receptor maintained its ability to strongly bind benzenesulfonate and p‐toluenesulfonate. This is interpreted in terms of suppression of the ability of the cavitand to form hydrogen bonds at the rim of the molecule due to replacement of the C2?H proton by a methyl group, while the hydrophobic pocket of the molecule maintains its binding abilities.     

Water‐Soluble Molecular Capsules: Self‐Assembly and Binding Properties

The self‐assembly and characterization of water‐soluble calix[4]arene‐based molecular capsules ( 1?2 ) is reported. The assemblies are the result of ionic interactions between negatively charged calix[4]arenes 1 a and 1 b , functionalized at the upper rim with amino acid moieties, and a positively charged tetraamidiniumcalix[4]arene 2 . The formation of the molecular capsules is studied by ¹H NMR spectroscopy, ESI mass spectrometry (ESI‐MS), and isothermal titration calorimetry (ITC). A molecular docking protocol was used to identify potential guest molecules for the self‐assembled capsule 1 a?2 . Experimental guest encapsulation studies indicate that capsule 1 a?2 is an effective host for both charged (N‐methylquinuclidinium cation) and neutral molecules (6‐amino‐2‐methylquinoline) in water.     

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     

Resorcinarene-based cavitands with chiral amino acid substituents for chiral amine recognition

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (), alanine undecyl resorcinarene acid () and glycine undecyl resorcinarene acid (), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of , , and with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary l-tartaric acid and the monoacid phthalyl alanine (). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary l-tartaric acid only binds one amine guest strongly. The simple compound , which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.     

Triterpenoid‐Based Self‐Healing Supramolecular Polymer Hydrogels Formed by Host–Guest Interactions

Pentacyclic triterpenoids, a class of naturally bioactive products having multiple functional groups, unique chiral centers, rigid skeletons, and good biocompatibility, are ideal building blocks for fabricating versatile supramolecular structures. In this research, the natural pentacyclic triterpenoid glycyrrhetinic acid (GA) was used as a guest molecule for β‐cyclodextrin (β‐CD) to form a GA/β‐CD (1:1) inclusion complex. By means of GA and β‐CD pendant groups in N,N′‐dimethylacrylamide copolymers, a supramolecular polymer hydrogel can be physically cross‐linked by host–guest interactions between GA and β‐CD moieties. Moreover, self‐healing of this hydrogel was observed and confirmed by step‐strain rheological measurements, whereby the maximum storage modulus occurred at a [GA]/[β‐CD] molar ratio of 1:1. Additionally, these polymers displayed outstanding biocompatibility. The introduction of a natural pentacyclic triterpenoid into a hydrogel system not only provides a biocompatible guest–host complementary GA/β‐CD pair, but also makes this hydrogel an attractive candidate for tissue engineering.     

Acid–Base Controllable Recognition Properties of a Highly Versatile Calix[6]crypturea

Versatile concave receptors with binding properties that can be controlled by external stimuli are rare. Herein, we report on a calix[6]crypturea ( 1 ) that features two different binding sites in close proximity, that is, a tris(2‐aminoethyl)amine (tren)‐based tris‐ureido cap that provides convergent hydrogen‐bond‐donor sites and a hydrophobic cavity suitable for the inclusion of organic guests. The binding properties of this heteroditopic receptor have been evaluated by NMR spectroscopic studies. Compound 1 behaves as a remarkably versatile host that strongly binds neutral molecules, anions, or contact ion pairs. Within each family of guests, compound 1 is able to discriminate between different guests with a high degree of selectivity. Indeed, neutral molecules that possess hydrogen‐bond donor and acceptor groups, chloride anions, and linear ammonium ions associated to F^? or Cl^? are particularly well recognized. In comparison with all the related receptors, compound 1 displays several unique features: 1) charged or neutral species are also recognized in polar or protic solvents, 2) thanks to the flexibility of the calixarene structure, induced‐fit processes allow the binding of large, biologically relevant ammonium salts such as neurotransmitters, and 3) the protonation of the basic cap leads to a positively charged receptor, 1? H⁺, which is reluctant to host anions and in which host properties are now governed by strong charge–dipole interactions with the guests. In other words, compound 1 presents an acid–base controllable tris‐ureido recognition site protected by a hydrophobic corridor that can select guests through induced‐fit processes. Thus, its versatile host properties can be allosterically controlled by protonation and selective guest‐switching processes are possible. To illustrate all these remarkable features, a sophisticated three‐pole supramolecular switch, based on the interconversion of host–guest systems displaying either charged or neutral guests, is described.     

Wide‐Ranging Host Capability of a PdII‐Linked M2L4 Molecular Capsule with an Anthracene Shell

This article reports that an M₂L₄ molecular capsule is capable of encapsulating various neutral molecules in quantitative yields. The capsule was obtained as a single product by mixing a small number of components; two Pd^II ions and four bent bispyridine ligands containing two anthracene panels. Detailed studies of the host capability of the Pd^II‐linked capsule revealed that spherical (e.g., paracyclophane, adamantanes, and fullerene C₆₀), planar (e.g., pyrenes and triphenylene), and bowl‐shaped molecules (e.g., corannulene) were encapsulated in the large spherical cavity, giving rise to 1:1 and 1:2 host–guest complexes, respectively. The volume of the encapsulated guest molecules ranged from 190 to 490 ų. Within the capsule, the planar guests adopt a stacked‐dimer structure and the bowl‐shaped guests formed an unprecedented concave‐to‐concave capsular structure, which are fully shielded by the anthracene shell. Competitive binding experiments of the capsule with a set of the planar guests established a preferential binding series for pyrenes≈phenanthrene>triphenylene. Furthermore, the capsule showed the selective formation of an unusual ternary complex in the case of triphenylene and corannulene.     

Photo‐ and Redox‐Active Dendritic Molecules with Soft,Layered Nanostructures

Molecules with one photoactive group (porphyrin) and multiple redox‐active groups (ferrocenes) are described. The molecules are based on dendritic frameworks, with the ferrocenyl groups attached at the “internal” positions and the porphyrin attached at the focal point, leading to a characteristic layer architecture. Molecules of up to the third generation were synthesized and examined. The results of ¹H NMR spectroscopy and fluorescence quenching indicated that the ferrocenyl groups at the second layer approach the core porphyrin most closely, which is consistent with the results of molecular‐dynamics simulations. The electrochemistry of the molecules was also examined in detail, and a new formula is proposed for the analysis of multiple‐electron transfer in these “redox‐pool” molecules.