Elucidating the Binding Mode of Sulfur- and Selenium-Based Cationic Chalcogen-Bond Donors.

For a comparison of the interaction modes of various chalcogen-bond donors, 2-chalcogeno-imidazolium salts have been designed, synthesized, and studied by single crystal X-ray diffraction, solution NMR and DFT as well as for their ability to act as activators in an SN1-type substitution reaction. Their interaction modes in solution were elucidated based on NMR diffusion and chemical shift perturbation experiments, which were supported by DFT-calculations. Our finding is that going from lighter to the heavier chalcogens, hydrogen bonding plays a less, while chalcogen bonding an increasingly important role for the coordination of anions. Anion-π interactions also show importance, especially for the sulfur and selenium derivatives.

Unlocking Photocatalytic Activity of Acridinium Salts by Anion-Binding Co-Catalysis.

The in situ generation of active photoredox organic catalysts upon anion-binding co-catalysis by making use of the ionic nature of common photosensitizers is reported. Hence, the merge of anion-binding and photocatalysis permitted the modulation of the photocatalytic activity of simple acridinium halide salts, building an effective anion-binding - photoredox ion pair complex able to promote a variety of visible light driven transformations, such as anti-Markovnikov addition to olefins, Diels-Alder and the desilylative C-C bond forming reactions. Anion-binding studies, together with steady-state and time-resolved spectroscopy analysis, supported the postulated ion pair formation between the thiourea hydrogen-bond donor organocatalyst and the acridinium salt, which proved essential for unlocking the photocatalytic activity of the photosensitizer.

Ion-Pairing Assemblies of Anion-Responsive π-Electronic Systems That Have Noncovalently Assisted Expanded Planar Region.

Arylethynyl-substituted dipyrrolyldiketone BF2 complexes as anion-responsive π-electronic molecules exhibited characteristic electronic properties derived from conformation changes upon anion binding, which caused an increase in UV/vis absorption and associated two-photon absorption. The anion complexes showed expanded planar regions assisted by intramolecular interactions, resulting in charge-by-charge ion-pairing assemblies in the solid state.

Cone Angles Quantify and Predict the Affinity and Reactivity of Anion Complexes between Trifluoroborates and Rigid Macrocycles.

Steric manipulation is a known concept in molecular recognition but there is currently no linear free energy relationship correlating sterics to the stability of receptor-anion complexes nor to the reactivity of the bound anion. By analogy to Tolman cone angles in cation coordination chemistry, we explore how to define and correlate cone angles of organo-trifluoroborates (R-BF3 -) to the affinities observed for cyanostar-anion binding. We extend the analogy to a rare investigation of the anion's reactivity and how it changes upon binding. The substituent on the anion is used to define the cone angle, θ. A series of 10 anions were studied including versions with ethynyl, ethylene, and ethyl substituents to tune steric bulk across the sp, sp2 and sp3 hybridized α-carbons bearing 0, 1 and 2 hydrogen atoms. A linear relationship between affinity and cone angle is observed for anions bearing substituents larger than the -BF3 - headgroup. This correlation predicted affinities of two new anions to within ±5 %. We explored how complexation affects the reactivity of fluoride exchange. The yield of fluoride transfer from R-BF3 - to Lewis acid triphenylborane is correlated with cone angle. We predict that other rigid macrocycles, like commercially available bambusuril, could follow these trends.

Tuning CH Hydrogen Bond-Based Receptors toward Picomolar Anion Affinity via the Inductive Effect of Distant Substituents.

Inspired by nature, artificial hydrogen bond-based anion receptors have been developed to achieve high anion selectivity; however, their binding affinity is usually low. The potency of these receptors is usually increased by the introduction of aryl substituents, which withdraw electrons from their binding site through the resonance effect. Here, we show that the polarization of the C(sp3 )-H binding site of bambusuril receptors, and thus their potency to bind anions, can be modulated by the inductive effect. The presence of electron-withdrawing groups on benzyl substituents of bambusurils significantly increases their binding affinities to halides, resulting in the strongest iodide receptor reported to date with an association constant greater than 1013  M-1 in acetonitrile. A Hammett plot showed that while the bambusuril affinity toward halides linearly increases with the electron-withdrawing power of their substituents, their binding selectivity remains essentially unchanged.

Gated, Selective Anion Exchange in Functionalized Self-Assembled Cage Complexes.

Appending functional groups to the exterior of Zn4 L4 self-assembled cages allows gated control of anion binding. While the unfunctionalized cages contain aryl groups in the ligand that can freely rotate, attaching inert functional groups creates a "doorstop", preventing rotation and slowing the guest exchange rate, even though the interiors of the host cavities are identically structured. The effects on anion exchange are subtle and depend on multiple factors, including anion size, the nature of the leaving anion, and the electron-withdrawing ability and steric bulk of the pendant groups. Multiple exchange mechanisms occur, and the nature of the external groups controls associative and dissociative exchange processes: these bulky groups affect both anion egress and ingress, introducing an extra layer of selectivity to the exchange. Small changes can have large effects: affinities for anions as similar as PF6 - and SbF6 - can vary by as much as 400-fold between identically sized cavities.

Steric Control over the Threading of Pyrophosphonates with One or Two Cyanostar Macrocycles during Pseudorotaxane Formation.

The supramolecular recognition of anions is increasingly harnessed to achieve the self-assembly of supramolecular architectures, ranging from cages and polymers to (pseudo)rotaxanes. The cyanostar (CS) macrocycle has previously been shown to form 2 : 1 complexes with organophosphate anions that can be turned into [3]rotaxanes by stoppering. Here we achieved steric control over the assembly of pseudorotaxanes comprising the cyanostar macrocycle and a thread that is based, for the first time, on organo-pyrophosphonates. Subtle differences in steric bulk on the threads allowed formation of either [3]pseudorotaxanes or [2]pseudorotaxanes. We demonstrate that the threading kinetics are governed by the steric demand of the organo-pyrophosphonates and in one case, slows down to the timescale of minutes. Calculations show that the dianions are sterically offset inside the macrocycles. Our findings broaden the scope of cyanostar-anion assemblies and may have relevance for the design of molecular machines whose directionality is a result of relatively slow slipping.

Pyrene-Containing Polyamines as Fluorescent Receptors for Recognition of PFOA in Aqueous Media.

The globally widespread perfluorooctanoic acid (PFOA) is a concerning environmental contaminant, with a possible toxic long-term effects on the environment and human health The development of sensible, rapid, and low-cost detection systems is a current change in modern environmental chemistry. In this context, two triamine-based chemosensors, L1 and L2, containing a fluorescent pyrene unit, and their Zn(II) complexes are proposed as fluorescent probes for the detection of PFOA in aqueous media. Binding studies carried out by means of fluorescence and NMR titrations highlight that protonated forms of the receptors can interact with the carboxylate group of PFOA, thanks to salt bridge formation with the ammonium groups of the aliphatic chain. This interaction induces a decrease in the fluorescence emission of pyrene at neutral and slightly acidic pH values. Similarly, emission quenching has also been observed upon coordination of PFOA by the Zn(II) complexes of the receptors. These results evidence that simple polyamine-based molecular receptors can be employed for the optical recognition of harmful pollutant molecules, such as PFOA, in aqueous media.

Visible-Light-Switchable Tellurium-Based Chalcogen Bonding: Photocontrolled Anion Binding and Anion Abstraction Catalysis.

Exploring new noncovalent bonding motifs with reversibly tunable binding affinity is of fundamental importance in manipulating the properties and functions of supramolecular self-assembly systems and materials. Herein, for the first time, we demonstrate a unique visible-light-switchable telluro-triazole/triazolium-based chalcogen bonding (ChB) system in which the Te moieties are connected by azobenzene cores. The binding strengths between these azo-derived ChB receptors and the halide anions (Cl- , Br- ) could be reversibly regulated upon irradiation by visible light of different wavelengths. The cis-bidentate ChB receptors exhibit enhanced halide anion binding ability compared to the trans-monodentate receptors. In particular, the telluro-triazolium-based ChB receptor can achieve both high and significantly photoswitchable binding affinities for halide anions, which enable it to serve as an efficient photocontrolled organocatalyst for ChB-assisted halide abstraction in a Friedel-Crafts alkylation benchmark reaction.

Mechanistic Insight into Anion-Binding Catalytic Living Cationic Polymerization.

Exploiting non-covalent interactions to catalyze challenging ionic polymerizations is an ambitious goal but is in its infancy. We recently demonstrated non-covalent anion-binding catalysis as an effective methodology to enable living cationic polymerization (LCP) of vinyl ethers in an environmentally benign manner. Here, we further elucidate the structure-reactivity relationships of the elaborately designed seleno-cyclodiphosph(V)azanes catalysts and the roles of anion-binding interactions by a combined theoretical DFT study and experimental study. The investigation suggests that the distinct cis-cyclodiphosph(V)azane framework combined with "selenium effect" and electron-withdrawing 3,5-(CF3 )2 -Phenyl substitution pattern in catalyst enables a critical contribution to accessing excellent stability, anion affinity and solubility under polymerization conditions. Thus, the catalyst could leverage anion-binding interactions to precisely control reversible and transient dormant-active species equilibrium, allowing it to dynamically bind, recognize and pre-organize propagating ionic species and monomer, thereby facilitating efficient chain propagation and minimizing irreversible chain transfer events under mild conditions. The more in-depth understanding of the mechanism for anion-binding catalytic LCP reported herein should help to guide future catalyst design and to extend this concept to broader polymerization systems where ionic species serve as crucial intermediates.

Exploiting the Catenane Mechanical Bond Effect for Selective Halide Anion Transmembrane Transport.

The first examples of [2]catenanes capable of selective anion transport across a lipid bilayer are reported. The neutral halogen bonding (XB) [2]catenanes were prepared via a chloride template-directed strategy in an unprecedented demonstration of using XB⋅⋅⋅anion interactions to direct catenane assembly from all-neutral components. Anion binding experiments in aqueous-organic solvent media revealed strong halide over oxoanion selectivity, and a marked enhancement in the chloride and bromide affinities of the catenanes relative to their constituent macrocycles. The catenanes additionally displayed an anti-Hofmeister binding preference for bromide over the larger iodide anion, illustrating the efficacy of employing sigma-hole interactions in conjunction with the mechanical bond effect to tune receptor selectivity. Transmembrane anion transport studies conducted in POPC LUVs revealed that the catenanes were more effective anion transporters than the constituent macrocycles, with high chloride over hydroxide selectivity, which is critical to potential therapeutic applications of anionophores. Remarkably these outperform existing acyclic halogen bonding anionophores with regards to this selectivity. Record chloride over nitrate anion transport selectivity was also observed. This represents a rare example of the direct translation of intrinsic anion binding affinities to anion transport behaviour, and demonstrates the key role of the catenane mechanical bond effect for enhanced anion transport selectivity.

Fine-Tuning Substrate-Catalyst Halogen-Halogen Interactions for Boosting Enantioselectivity in Halogen-Bonding Catalysis.

A new approach towards highly enantioselective halogen-bonding catalysis has been developed. To circumvent the intrinsic issues of the nature of the halogen-bond (XB) and the resultant unresolved limitations in asymmetric catalysis, fine-tuned halogen-halogen interactions between the substrate and XB-donor were designed to preorganize the substrate in the catalyst's cavity and boost enantiocontrol. The present strategy exploits both the electron cloud (Lewis base site) and the sigma (σ)-hole site of the halogen substituent of the substrates to form a tight catalyst-substrate-counteranion chiral complex, thus enabling a controlled induction of high levels of chirality transfer. Remarkable enantioselectivities of up to 95 : 5 e.r. (90 % ee) have been achieved in a model dearomatization reaction of halogen-substituted (iso)quinolines with tetrakis-iodotriazole multidentate anion-binding catalysts.

A Bidentate Ligand Featuring Ditopic Lewis Acids in the Second Sphere for Selective Substrate Capture and Activation.

We present a ligand platform featuring appended ditopic Lewis acids to facilitate capture/activation of diatomic substrates. We show that incorporation of two 9-borabicyclo[3.3.1]nonane (9-BBN) units on a single carbon tethered to a pyridine pyrazole scaffold maintains a set of unquenched nitrogen donors available to coordinate FeII , ZnII , and NiII . Using hydride ion affinity and competition experiments, we establish an additive effect for ditopic secondary sphere boranes, compared to the monotopic analogue. These effects are exploited to achieve high selectivity for binding NO2 - in the presence of competitive anions such as F- and NO3 - . Finally, we demonstrate hydrazine capture within the second-sphere of metal complexes, followed by unique activation pathways to generate hydrazido and diazene ligands on Zn and Fe, respectively.

The unique Phe-His dyad of 2-ketopropyl coenzyme M oxidoreductase/carboxylase selectively promotes carboxylation and S-C bond cleavage.

The 2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) enzyme is the only member of the disulfide oxidoreductase (DSOR) family of enzymes, which are important for reductively cleaving S-S bonds, to have carboxylation activity. 2-KPCC catalyzes the conversion of 2-ketopropyl-coenzyme M to acetoacetate, which is used as a carbon source, in a controlled reaction to exclude protons. A conserved His-Glu motif present in DSORs is key in the protonation step; however, in 2-KPCC, the dyad is substituted by Phe-His. Here, we propose that this difference is important for coupling carboxylation with C-S bond cleavage. We substituted the Phe-His dyad in 2-KPCC to be more DSOR like, replacing the phenylalanine with histidine (F501H) and the histidine with glutamate (H506E), and solved crystal structures of F501H and the double variant F501H_H506E. We found that F501 protects the enolacetone intermediate from protons and that the F501H variant strongly promotes protonation. We also provided evidence for the involvement of the H506 residue in stabilizing the developing charge during the formation of acetoacetate, which acts as a product inhibitor in the WT but not the H506E variant enzymes. Finally, we determined that the F501H substitution promotes a DSOR-like charge transfer interaction with flavin adenine dinucleotide, eliminating the need for cysteine as an internal base. Taken together, these results indicate that the 2-KPCC dyad is responsible for selectively promoting carboxylation and inhibiting protonation in the formation of acetoacetate.

Putting Anion-π Interactions at Work for Catalysis.

Since its discovery two decades ago, anion-π interaction has been increasingly recognized as an important driving force. Extensive theoretical and experimental efforts on the ground-state anion-π binding and recognition have laid the bases for exploring its relevance in catalysis. Accordingly, the concept of "anion-π catalysis" that employing an electron-deficient π surface (π-acidic surface) for anionic reaction intermediate and transition state stabilization has emerged. This article shortly reviews the emergence and development of this concept, aiming to provide an emphasis on the general concept and key progress in this exciting area. To highlight the essential contribution of anion-π interactions, the contents are organized according to their role engaged in catalytic process, for example from both ground-state and transition-state stabilization to solely transition-state stabilization, mainly by a single π-face, and to cooperative π-face activation. A concluding remark and outlook on future development of this field is also given.

Mutation of external glutamate residue reveals a new intermediate transport state and anion binding site in a CLC Cl-/H+ antiporter.

The CLC family of proteins are involved in a variety of physiological processes to control cellular chloride concentration. Two distinct classes of CLC proteins, Cl- channels and Cl-/H+ antiporters, have been functionally and structurally investigated over the last several decades. Previous studies have suggested that the conformational heterogeneity of the critical glutamate residue, Gluex, could explain the transport cycle of CLC-type Cl-/H+ antiporters. However, the presence of multiple conformations (Up, Middle, and Down) of the Gluex has been suggested from combined structural snapshots of 2 different CLC antiporters: CLC-ec1 from Escherichia coli and cmCLC from a thermophilic red alga, Cyanidioschyzon merolae Thus, we aimed to investigate further the heterogeneity of Gluex-conformations in CLC-ec1, the most deeply studied CLC antiporter, at both functional and structural levels. Here, we show that the crystal structures of the Gluex mutant E148D and wild-type CLC-ec1 with varying anion concentrations suggest a structural intermediate, the "Midlow" conformation. We also found that an extra anion can be located above the external Cl--binding site in the E148D mutant when the anion concentration is high. Moreover, we observed that a carboxylate in solution can occupy either the external or central Cl--binding site in the ungated E148A mutant using an anomalously detectable short carboxylic acid, bromoacetate. These results lend credibility to the idea that the Gluex can take at least 3 distinct conformational states during the transport cycle of a single CLC antiporter.

Anion-Sensing Properties of Cyclopentaphenylalanine.

Cyclic pentaphenylalanine was studied as an efficient anion sensor for halides, thiocyanate and oxoanions in acetonitrile and methanol. Stability constants of the corresponding complexes were determined by means of fluorimetric, spectrophotometric, 1H NMR, and microcalorimetric titrations. A detailed structural overview of receptor-anion complexes was obtained by classical molecular dynamics (MD) simulations. The results of 1H NMR and MD studies indicated that the bound anions were coordinated by the amide groups of cyclopeptide, as expected. Circular dichroism (CD) titrations were also carried out in acetonitrile. To the best of our knowledge, this is the first example of the detection of anion binding by cyclopeptide using CD spectroscopy. The CD spectra were calculated from the structures obtained by MD simulations and were qualitatively in agreement with the experimental data. The stoichiometry of almost all complexes was 1:1 (receptor:anion), except for dihydrogen phosphate where the binding of dihydrogen phosphate dimer was observed in acetonitrile. The affinity of the cyclopeptide receptor was correlated with the structure of anion coordination sphere, as well as with the solvation properties of the examined solvents.

Highly Efficient and Selective Recognition of Dicyanoaurate(I) by a Bambusuril Macrocycle in Water.

Dicyanoaurate(I) anion, [Au(CN)2 ]- , plays a central role in the current industrial production of gold, as its extraction from crude ore samples represents the most money-consuming step. Herein, we present the strongest host-guest recognition of dicyanoaurate anion using the bambusuril receptor in water, a highly competitive solvent. The micromolar stability of such a complex facilitated the up to date most efficient supramolecular stripping of dicyanoaurate from activated carbon at ambient temperature. Thermodynamic characteristics of bambusuril binding with [Au(CN)2 ]- differing from binding of other inorganic chaotropic anions are rationalized, as well as the bambusuril selectivity for [Au(CN)2 ]- over [Ag(CN)2 ]- .

Entropy Versus Enthalpy Controlled Temperature/Redox Dual-Triggered Cages for Selective Anion Encapsulation and Release.

New C3 -symmetric imidazole ligands were designed with phosphine and phosphine oxide linkers (LP and LPO , respectively) to demonstrate a dual-triggered dynamic closed coordination cage. Both LP and LPO form discrete Zn4 L4 -closed cages (1P and 1PO , respectively) with excellent selectively for BPh4 - , whereas 1P and 1PO encapsulate neither a slightly larger size anion [B(C6 H4 CH3 )4 - ] nor smaller size anions (BF4 - , PF6 - , SbF6 - , and OSO2 CF3 - ). 1PO exhibits more negative enthalpy and entropy changes upon anion encapsulation, thus releasing almost all of the encapsulated anions at high temperature (343 K) (trigger 1: BPh4 - ⊂1PO ← → 1PO +BPh4 - ). In contrast 1P has less negative enthalpy and entropy changes, thus preserving the captured anion over a wide range of temperatures (298 K to 343 K). The 1P cage can be quantitatively oxidized to the 1PO cage by a mild oxidant (Ox.=H2 O2 ), and therefore the captured anion can be released by a redox triggering event (trigger 2: BPh4 - ⊂1P +Ox.→1PO +BPh4 - ).

Bambusuril Macrocycles as Mediators of Supramolecular Interactions: Application to the Europium Cage Helicate.

Herein, it is shown how bambusurils can be used for tuning and/or characterizing supramolecular systems. Indeed, the addition of bambusurils as anion scavengers to metal-mediated self-assemblies allows manipulation of the subtle equilibria in the given system. This is demonstrated for the case of the tetranuclear europium helical cage, which is well suited to different applications. Among the reported results, experimental evidence is provided showing that perchlorate and triflate anions act as a molecular template for the cage assembly. The complexation of inorganic anions with neutral bambusurils resulted in bulky non-coordinating counterions that may trigger the self-assembly process or stimulate specific interactions between components. Moreover, bambusuril was able to selectively remove coordinating nitrates from the mixture with non-coordinating anions, enabling the regeneration of the helical cage.