C vs N: Which End of the Cyanide Anion Is a Better Hydrogen Bond Acceptor?

The ability of the C and N ends of the cyanide anion (CN^–) as acceptors of hydrogen bonds, an experimentally difficult problem, has been computationally examined in this study. Structures obtained in our previous work involving cyanide binding within the cavity of a triazolophane macrocycle (<i>Chem.Eur. J</i>. <b>2011</b>, <i>17</i>, 9123–9129) were used to analyze the problem. Three different approaches involving (a) breakdown of the triazolophane into smaller components, (b) population analyses, and (c) ion–dipole analyses helped demonstrate that the N terminus of cyanide is a slightly better hydrogen bond acceptor than the C terminus even though it is not the site of protonation or covalent bond formation. This outcome reflects a competition between the preference for noncovalent interactions at the nitrogen and covalent bond formation at the carbon

Hydrophobic Collapse of Foldamer Capsules Drives Picomolar-Level Chloride Binding in Aqueous Acetonitrile Solutions

Aqueous media are competitive environments in which to perform host–guest chemistry, particularly when the guest is highly charged. While hydrophobic binding is a recognized approach to this challenge in which apolar pockets can be designed to recognize apolar guests in water, complementary strategies are required for hydrophilic anions like chloride. Here, we present evidence of such an alternative mechanism, used everyday by proteins yet rare for artificial receptors, wherein hydrophobic interactions are shown to be responsible for organizing and stabilizing an aryl-triazole foldamer to help extract hydrophilic chloride ions from increasingly aqueous solutions. Therein, a double-helical complex gains stability upon burial of ∼80% of the π surfaces that simultaneously creates a potent, solvent-excluding microenvironment for hydrogen bonding. The chloride’s overall affinity to the duplex is substantial in 25% water v/v in acetonitrile (log β₂ = 12.6), and it remains strong (log β₂ = 13.0) as the water content is increased to 50%. With the rise in predictable designs of abiological foldamers, this water-assisted strategy can, in principle, be utilized for binding other hydrophilic guests

Hydrophobic Collapse of Foldamer Capsules Drives Picomolar-Level Chloride Binding in Aqueous Acetonitrile Solutions

Aqueous media are competitive environments in which to perform host–guest chemistry, particularly when the guest is highly charged. While hydrophobic binding is a recognized approach to this challenge in which apolar pockets can be designed to recognize apolar guests in water, complementary strategies are required for hydrophilic anions like chloride. Here, we present evidence of such an alternative mechanism, used everyday by proteins yet rare for artificial receptors, wherein hydrophobic interactions are shown to be responsible for organizing and stabilizing an aryl-triazole foldamer to help extract hydrophilic chloride ions from increasingly aqueous solutions. Therein, a double-helical complex gains stability upon burial of ∼80% of the π surfaces that simultaneously creates a potent, solvent-excluding microenvironment for hydrogen bonding. The chloride’s overall affinity to the duplex is substantial in 25% water v/v in acetonitrile (log β₂ = 12.6), and it remains strong (log β₂ = 13.0) as the water content is increased to 50%. With the rise in predictable designs of abiological foldamers, this water-assisted strategy can, in principle, be utilized for binding other hydrophilic guests

Programmed Negative Allostery with Guest-Selected Rotamers Control Anion–Anion Complexes of Stackable Macrocycles

A new rotamer-based strategy for negative allostery has been used to control host–host interactions and product yield upon anion complexation. Coassembly of anion dimers as guests inside two cyanostar macrocycles drives selection of one rotamer in which all ten steric groups get directed outward to destabilize triply stacked macrocycles. A large entropy penalty (Δ<i>S</i>) is quantified upon anion binding when the multiple dynamic rotamers collapse down to one

Double Switching of Two Rings in Palindromic [3]Pseudorotaxanes: Cooperativity and Mechanism of Motion

The existence of two rings in [3]­pseudorotaxanes presents opportunities for those rings to undergo double switching and cooperative mechanical coupling. To investigate this capability, we identified a new strategy for bringing two rings into contact with each other and conducted mechanistic studies to reveal their kinetic cooperativity. A redox-active tetrazine ligand bearing two binding sites was selected to allow for two mobile copper­(I) macrocycle ring moieties to come together. To realize this switching modality, ligands were screened against their ability to serve as stations on which the rings are initially parked, ultimately identifying 5,5′-dimethyl-2,2′-bipyridine. The kinetics of switching a macrocycle in a <i>single</i>-site [2]­pseudorotaxane between bipyridine and <i>single</i>-site tetrazine stations were examined using electrochemistry. The forward movement was rate-limited by the bimolecular reaction between reduced tetrazine and bipyridine [2]­pseudorotaxane. Two bipyridines were then used with a <i>double</i>-site tetrazine to verify double switching of two rings. Our results indicated stepwise movements, with the first ring moving 4 times more frequently (faster) than the second. While this behavior is indicative of <i>anti</i>cooperative kinetics, positive thermodynamic cooperativity sets the two rings in motion even though just one tetrazine is reduced with one electron. Double switching in this [3]­pseudorotaxane uniquely demonstrates how a series of independent thermodynamic states and kinetic paths govern an apparently simple mechanical motion

Polarized Naphthalimide CH Donors Enhance Cl^– Binding within an Aryl-Triazole Receptor

The dipolar character of 1,8-naphthalimide together with polarization of the C⁴–H and C⁵–H donors has been utilized in receptor <b>1</b> to effectively bind chloride alongside triazole and phenylene units. The Cl^– binding strength of <b>1</b> shows that the naphthalimide provides greater anion stabilization than an unactivated phenylene, and DFT calculations show that its collinear donor array can be a “urea-like” analog for CH···anion interactions

Selective Anion-Induced Crystal Switching and Binding in Surface Monolayers Modulated by Electric Fields from Scanning Probes

Anion-selective (Br^– and I^–) and voltage-driven crystal switching between two differently packed phases (α ⇆ β) was observed in 2D crystalline monolayers of aryl-triazole receptors ordered at solution–graphite interfaces. Addition of Br^– and I^– was found to stimulate the α → β phase transformation and to produce ion binding to the β phase assembly, while Cl^– and BF₄^– addition retained the α phase. Unlike all other surface assemblies of either charged molecules or ion-templated 2D crystallization of metal-ligand or receptor-based adsorbates, the polarity of the electric field between the localized scanning tip and the graphite substrate was found to correlate with phase switching: β → α is driven at −1.5 V, while α → β occurs at +1.1 V. Ion-pairing between the countercations and the guest anions was also observed. These observations are supported by control studies including variation of anion species, relative anion concentration, surface temperature, tip voltage, and scanning time

Arginine–Phosphate Recognition Enhanced in Phospholipid Monolayers at Aqueous Interfaces

Due to the growing world population, there is an ever-increasing need to develop better receptors to recover and recycle phosphate for use in agricultural processes. This need is driven by agricultural demand and environmental concerns because phosphate eutrophication has a damaging effect on fresh water supplies by fueling algal blooms. The air/water interface provides a unique region with a dielectric constant (ε) that diminishes from high in bulk water (ε = 80) to significantly lower (e.g., ε < 40) near the monolayer surface to potentially enhance affinities during molecular recognition. The work presented here uses a model system of phosphate binding to an amino acid, arginine, and utilizes the interfacial properties of the phospholipid monolayer, 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphatidic acid, as the phosphate source to quantify binding. Employing arginine as a probe molecule allows for the evaluation of its guanidinium moiety for phosphate chelation. Surface pressure–area isotherms from Langmuir monolayer studies, and the corresponding infrared reflection absorption spectroscopy, were used along with Brewster angle microscopy for in situ determination of molecular binding interactions and the surface binding constants of the phosphate–guanidinium complex, which are shown here to be greater than 10³ M^–1. The binding constant in bulk solution, determined by NMR titrations of phosphate and arginine, is determined to be on the order of 0.1 M^–1. The greater than 10 000-fold increase from the bulk aqueous solution to the air/water interface reveals that the interface provides a region of enhanced binding affinity

Cyanostar: C–H Hydrogen Bonding Neutral Carrier Scaffold for Anion-Selective Sensors

Cyanostar, a pentagonal macrocyclic compound with an electropositive cavity, binds anions with CH-based hydrogen bonding. The large size of the cyanostar’s cavity along with its planarity favor formation of 2:1 sandwich complexes with larger anions, like perchlorate, ClO₄^–, relative to the smaller chloride. We also show that cyanostar is selective for ClO₄^– over the bulky salicylate anions by using NMR titration studies to measure affinity. The performance of this novel macrocycle as an anion ionophore in membrane ion sensors was evaluated. The cyanostar-based electrodes demonstrated a Nernstian response toward perchlorate with selectivity patterns distinctly different from the normal Hofmeister series. Different membrane compositions were explored to identify the optimum concentrations of the ionophore, plasticizer, and lipophilic additive that give rise to the best perchlorate selectivity. Changing the concentration of the lipophilic additive tridodecylmethylammonium chloride was found to impact the selectivity pattern and the analytical dynamic range of the electrodes. The high selectivity of the cyanostar sensors and their detection limit could enable the determination of ClO₄^– in contaminated environmental samples. This novel class of macrocycle provides a suitable scaffold for designing various anion-selective ionophores by altering the size of the central cavity and its functionalization

An Overlooked yet Ubiquitous Fluoride Congenitor: Binding Bifluoride in Triazolophanes Using Computer-Aided Design

Despite its ubiquity during the binding and sensing of fluoride, the role of bifluoride (HF₂^–) and its binding properties are almost always overlooked. Here, we give one of the first examinations of bifluoride recognition in which we use computer-aided design to modify the cavity shape of triazolophanes to better match with HF₂^–. Computational investigation indicates that HF₂^– and Cl^– should have similar binding affinities to the parent triazolophane <i>in the gas phase</i>. Evaluation of the binding geometries revealed a preference for binding of the linear HF₂^– along the north–south axis with a smaller Boltzmann weighted population aligned east–west and all states being accessed rapidly through in-plane precessional rotations of the anion. While the ¹H NMR spectroscopy studies are consistent with the calculated structural aspects, binding affinities <i>in solution</i> were determined to be significantly smaller for the bifluoride than the chloride. Computed geometries suggested that a 20° tilting of the bifluoride (stemming from the cavity size) could account for the 25-fold difference between the two binding affinities, HF₂^– < Cl^–. Structural variations to the triazolophane’s geometry and electronic modifications to the network of hydrogen bond donors were subsequently screened in a stepwise manner using density functional theory calculations to yield a final design that eliminates the tilting. Correspondingly, the bifluoride’s binding affinity (<i>K</i> ∼ 10⁶ M^–1) increased and was also found to remain equal to chloride <i>in the gas and solution phases</i>. The new oblate cavity appeared to hold the HF₂^– in a single east–west arrangement. Our findings demonstrate the promising ability of computer-aided design to fine-tune the structural and electronic match in anion receptors as a means to control the arrangement and binding strength of a desired guest