Molecular‐Recognition‐Assisted pKa Shifts and Metal‐Ion‐Induced Fluorescence Regeneration in p‐Sulfonatocalix[6]arene‐Encapsulated Acridine

The host–guest interactions of cationic (AcH⁺) and neutral (Ac) forms of the dye acridine with the macrocyclic host p‐sulfonatocalix[6]arene (SCX6) were investigated by using ground‐state absorption, steady‐state and time‐resolved fluorescence, and NMR measurements. The cationic form undergoes significant complexation with SCX6 (K_eq=2.5×10⁴ M ^?1), causing a sharp decrease in the fluorescence intensity and severe quenching in the excited‐state lifetime of the dye. The strong binding of the AcH⁺ form of the dye with SCX6 is attributed to ion–ion interactions involving the sulfonato groups (SO₃^?) of SCX6 and the positively charged AcH⁺ at pH of approximately 4.3. Whereas, the neutral Ac form of the dye undergoes weak complexation with SCX6 (K_eq=0.9×10³ M ^?1) and the binding constant is lowered by one order of magnitude compared with that of the SCX6–AcH⁺ system. The strong affinity of SCX6 to the protonated form leads to a large upward pK_a shift (≈2 units) in the dye. In contrast, strong emission quenching upon SCX6 interaction and the regeneration of fluorescence intensity of the dye in the presence of Gd³⁺ through competitive binding have also been demonstrated.     

Modulating the Binding of Polycyclic Aromatic Hydrocarbons Inside a Hexacationic Cage by Anion–π Interactions

We report the template‐directed synthesis of BlueCage⁶⁺, a macrobicyclic cyclophane composed of six pyridinium rings fused with two central triazines and bridged by three paraxylylene units. These moieties endow the cage with a remarkably electron‐poor cavity, which makes it a powerful receptor for polycyclic aromatic hydrocarbons (PAHs). Upon forming a 1:1 complex with pyrene in acetonitrile, however, BlueCage?6 PF₆ exhibits a lower association constant K_a than its progenitor ExCage?6 PF₆. A close inspection reveals that the six PF₆^? counterions of BlueCage⁶⁺ occupy the cavity in a fleeting manner as a consequence of anion–π interactions and, as a result, compete with the PAH guests. This conclusion is supported by a one order of magnitude increase in the K_a value for pyrene in BlueCage⁶⁺ when the PF₆^? counterions are replaced by much bulkier anions. The presence of anion–π interactions is supported by X‐ray crystallography, and confirms the presence of a PF₆^? counterion inside its cavity.     

Self‐Assembly and Disassembly of Vesicles as Controlled by Anion–π Interactions

Anion–π interactions have been widely studied as new noncovalent driving forces in supramolecular chemistry. However, self‐assembly induced by anion–π interactions is still largely unexplored. Herein we report the formation of supramolecular amphiphiles through anion–π interactions, and the subsequent formation of self‐assembled vesicles in water. With the π receptor 1 as the host and anionic amphiphiles, such as sodium dodecylsulfate (SDS), sodium laurate (SLA), and sodium methyl dodecylphosphonate (SDP), as guests, the sequential formation of host–guest supramolecular amphiphiles and self‐assembled vesicles was demonstrated by SEM, TEM, DLS, and XRD techniques. The intrinsic anion–π interactions between 1 and the anionic amphiphiles were confirmed by crystal diffraction, HRMS analysis, and DFT calculations. Furthermore, the controlled disassembly of the vesicles was promoted by competing anions, such as NO₃^?, Cl^?, and Br^?, or by changing the pH value of the medium.     

Recognition Properties and Self‐assembly of Planar [M(2‐pyridyl‐1,2,3‐triazole)2]2+ Metallo‐ligands

Molecular recognition continues to be an area of keen interest for supramolecular chemists. The investigated [M( L )₂]²⁺ metallo‐ligands (M=Pd^II, Pt^II, L =2‐(1‐(pyridine‐4‐methyl)‐1 H‐1,2,3‐triazol‐4‐yl)pyridine) form a planar cationic panel with vacant pyridyl binding sites. They interact with planar neutral aromatic guests through π–π and/or metallophilic interactions. In some cases, the metallo‐ligands also interacted in the solid state with Ag^I either through coordination to the pendant pyridyl arms, or through metal–metal interactions, forming coordination polymers. We have therefore developed a system that reliably recognises a planar electron‐rich guest in solution and in the solid state, and shows the potential to link the resultant host–guest adducts into extended solid‐state structures. The facile synthesis and ready functionalisation of 2‐pyridyl‐1,2,3‐triazole ligands through copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) “click” chemistry should allow for ready tuning of the electronic properties of adducts formed from these systems.     

Self‐Assembled Tetragonal Prismatic Molecular Cage Highly Selective for Anionic π Guests

The metal‐directed supramolecular synthetic approach has paved the way for the development of functional nanosized molecules. In this work, we report the preparation of the new nanocapsule 3? (CF₃SO₃)₈ with a A₄B₂ tetragonal prismatic geometry, where A corresponds to the dipalladium hexaazamacrocyclic complex Pd‐1 , and B corresponds to the tetraanionic form of palladium 5,10,15,20‐tetrakis(4‐carboxyphenyl)porphyrin ( 2 ). The large void space of the inner cavity and the supramolecular affinity for guest molecules towards porphyrin‐based hosts converts this nanoscale molecular 3D structure into a good candidate for host–guest chemistry. The interaction between this nanocage and different guest molecules has been studied by means of NMR, UV/Vis, ESI‐MS, and DOSY experiments, from which highly selective molecular recognition has been found for anionic, planar‐shaped π guests with association constants (K_a) higher than 10⁹ M ^?1, in front of non‐interacting aromatic neutral or cationic substrates. DFT theoretical calculations provided insights to further understand this strong interaction. Nanocage 3? (CF₃SO₃)₈ can not only strongly host one single molecule of M(dithiolene)₂ complexes (M=Au, Pt, Pd, and Ni), but also can finely tune their optical and redox properties. The very simple synthesis of both the supramolecular cage and the building blocks represents a step forward for the development of polyfunctional supramolecular nanovessels, which offer multiple applications as sensors or nanoreactors.     

Host–guest interactions between octa acid and cations/nucleobases

The nature of host–guest interaction in between octa acid cavitand (OA) and some representative cationic guests (Li⁺, Na⁺, K⁺, Be⁺², Mg⁺², Ca⁺², Li₃O⁺, Na₃O⁺, K₃O⁺) as well as heterocyclic moieties like [adenine (A), guanine (G), cytosine (C), thymine (T), uracil (U), and tetrathiafulvalene (TTF)] has been examined with the aid of density functional theory (DFT)‐based computations. Thermochemical results indicate that all the guests bind with OA in a thermodynamically favorable fashion at 298.15 K temperature and one atmospheric pressure. OA exhibits high selectivity in binding the lighter cations/metal cluster cations as compared to the heavier congeners along each given series. Moreover, OA exhibits enhanced affinity as well as selectivity in binding A/G/TTF molecules as compared to C/T/U. Noncovalent interaction and energy decomposition analyses reveal that in addition to the van der Waals interaction, significant contribution from electrostatic as well as orbital interactions dictate the outcome in all the host–guest complexes. Time dependent DFT calculations have been carried out to assess the role of the guests in tuning the electronic properties as well as absorption spectrum of OA. © 2017 Wiley Periodicals, Inc.     

Thermodynamic study on molecular association of some organic dyestuffs in aqueous solution

The temperature effects on the absorption spectra of acridine orange and methylene blue in aqueous solution at various concentrations have been observed, and it was found that the increase in temperature has an effect on the spectra similar to that of the dilution. The heats of dimerization of the dyestuffs in aqueous solution have been measured directly by the calorimetric titration method, and ΔH_d for acridine orange and methylene blue were found to be ?49.6 and ?83.3 kJ mol^?1, respectively. The entropy of dimerization values were also calculated to be ΔS_d = ?54.9 and ?211.6 J K^?1 mol^?1 for acridine orange and methylene blue, respectively. It has been concluded that the stacking interactions are primarily responsible for the self-association of the dye molecules.     

From Packed “Sandwich” to “Russian Doll”: Assembly by Charge‐Transfer Interactions in Cucurbit[10]uril

As the host possessing the largest cavity in the cucurbit[n]uril (CB[n]) family, CB[10] has previously displayed unusual recognition and assembly properties with guests but much remains to be explored. Herein, we present the recognition properties of CB[10] toward a series of bipyridinium guests including the tetracationic cyclophane known as blue box along with electron‐rich guests and detail the influence of encapsulation on the charge‐transfer interactions between guests. For the mono‐bipyridinium guest (methylviologen, MV ²⁺), CB[10] not only forms 1:1 and 1:2 inclusion complexes, but also enhances the charge‐transfer interactions between methylviologen and dihydroxynaphthalene ( HN ) by mainly forming the 1:2:1 packed “sandwich” complex (CB[10] ? 2 MV ²⁺ ?HN ). For guest 1 with two bipyridinium units, an interesting conformational switching from linear to “U” shape is observed by adding catechol to the solution of CB[10] and the guest. For the tetracationic cyclophane‐blue box, CB[10] forms a stable 1:1 inclusion complex; the two bipyridinium units tilt inside the cavity of CB[10] according to the X‐ray crystal structure. Finally, a supramolecular “Russian doll” was built up by threading a guest through the cavities of both blue box and CB[10].     

A Tunable Cyclic Container: Guest‐Induced Conformational Switching,Efficient Guest Exchange,and Selective Isolation of C70 from a Fullerene Mixture

An adaptable cyclic porphyrin dimer with highly flexible linkers has been used as an artificial molecular container that can efficiently encapsulate various aromatic guests (TCNQ/C₆₀/C₇₀) through strong π–π interactions by adjusting its cavity size and conformation. The planar aromatic guest (TCNQ) can be easily and selectively exchanged with larger aromatic guests (C₆₀/C₇₀). During the guest‐exchange process, the two porphyrin rings switch their relative orientation according to the size and shape of the guests. This behavior of the cyclic container has been thoroughly investigated by using UV/Vis spectroscopy, NMR spectroscopy, and X‐ray crystal structure determination of the host–guest assemblies. The electrochemical and photophysical studies demonstrated the occurrence of photoinduced electron transfer from bisporphyrin to TCNQ/C₆₀/C₇₀ in the respective host–guest assemblies. The cyclic host can form complexes with C₆₀ and C₇₀ with association constants of (2.8±0.2)×10⁵ and (1.9±0.3)×10⁸ m ⁻¹, respectively; the latter value represents the highest binding affinity for C₇₀ reported so far for zinc(II) bisporphyrinic receptors. This high selectivity for the binding of C₇₀ versus C₆₀ allows the easy extraction and efficient isolation of C₇₀ from a C₆₀/C₇₀ fullerene mixture. Experimental evidence was substantiated by DFT calculations.     

PI by NMR: Probing CH–π Interactions in Protein–Ligand Complexes by NMR Spectroscopy

While CH–π interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH–π interactions in drug–protein complexes. Herein, we present a fast and reliable methodology called PI (π interactions) by NMR, which can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino‐acid side‐chain labeling with ¹H‐¹³C NMR, we are able to identify specific protein protons of side‐chains engaged in CH–π interactions with aromatic ring systems of a ligand, based solely on ¹H chemical‐shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH–π interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual π interactions rather than averaged measures of all interactions.     

Construction of π‐Surface‐Metalated Pillar[5]arenes which Bind Anions via Anion–π Interactions

By simple ligand exchange of the cationic transition‐metal complexes [(Cp*)M(acetone)₃](OTf)₂ (Cp*=pentamethylcyclopentadienyl and M=Ir or Rh) with pillar[5]arene, mono‐ and polynuclear pillar[5]arenes, a new class of metalated host molecules, is prepared. Single‐crystal X‐ray analysis shows that the charged transition‐metal cations are directly bound to the outer π‐surface of aromatic rings of pillar[5]arene. One of the triflate anions is deeply embedded within the cavity of the trinuclear pillar[5]arenes, which is different to the host–guest behavior of most pillar[5]arenes. DFT calculation of the electrostatic potential revealed that the metalated pillar[5]arenes featured an electron‐deficient cavity due to the presence of the electron‐withdrawing transition metals, thus allowing encapsulation of electron‐rich guests mainly driven by anion–π interactions.     

Enolate Stabilization by Anion–π Interactions: Deuterium Exchange in Malonate Dilactones on π‐Acidic Surfaces

Of central importance in chemistry and biology, enolate chemistry is an attractive topic to elaborate on possible contributions of anion–π interactions to catalysis. To demonstrate the existence of such contributions, experimental evidence for the stabilization of not only anions but also anionic intermediates and transition states on π‐acidic aromatic surfaces is decisive. To tackle this challenge for enolate chemistry with maximal precision and minimal uncertainty, malonate dilactones are covalently positioned on the π‐acidic surface of naphthalenediimides (NDIs). Their presence is directly visible in the upfield shifts of the α‐protons in the ¹H NMR spectra. The reactivity of these protons on π‐acidic surfaces is measured by hydrogen–deuterium (H–D) exchange for 11 different examples, excluding controls. The velocity of H–D exchange increases with π acidity (NDI core substituents: SO₂R>SOR>H>OR>OR/NR₂>SR>NR₂). The H–D exchange kinetics vary with the structure of the enolate (malonates>methylmalonates, dilactones>dithiolactones). Moreover, they depend on the distance to the π surface (bridge length: 11–13 atoms). Most importantly, H–D exchange depends strongly on the chirality of the π surface (chiral sulfoxides as core substituents; the crystal structure of the enantiopure (R,R,P)‐macrocycle is reported). For maximal π acidity, transition‐state stabilizations up to ?18.8 kJ mol^?1 are obtained for H–D exchange. The Brønsted acidity of the enols increases strongly with π acidity of the aromatic surface, the lowest measured pK_a=10.9 calculates to a ΔpK_a=?5.5. Corresponding to the deprotonation of arginine residues in neutral water, considered as “impossible” in biology, the found enolate–π interactions are very important. The strong dependence of enolate stabilization on the unprecedented seven‐component π‐acidity gradient over almost 1 eV demonstrates quantitatively that such important anion–π activities can be expected only from strong enough π acids.     

Reversible reduction drives anion ejection and C60 binding within an FeII4L6 cage

Fe^II₄L₆ tetrahedral cage 1 was prepared from a redox-active dicationic naphthalenediimide (NDI) ligand. The +20 charge of the cage makes it a good host for anionic guests, with no binding observed for neutral aromatic molecules. Following reduction by Cp₂Co, the cage released anionic guests; subsequent oxidation by AgNTf₂ led to re-uptake of anions. In its reduced form, however, 1 was observed to bind neutral C₆₀. The fullerene guest was subsequently ejected following cage re-oxidation. The guest release process was found to be facilitated by anion-mediated transport from organic to aqueous solution. Cage 1 thus employs electron transfer as a stimulus to control the uptake and release of both neutral and charged guests, through distinct pathways.

Fe^II₄L₆ cage 1 binds anionic guests but not neutral guests. In its reduced form, the cage can bind neutral C₆₀. Reduction and oxidation of the cage could thus be used as a stimulus to control the uptake and release of both neutral and charged guests.     

Unexpectedly strong anion–π interactions on the graphene flakes

Interactions of anions with simple aromatic compounds have received growing attention due to their relevancy in various fields. Yet, the anion–π interactions are generally very weak, for example, there is no favorable anion–π interaction for the halide anion F^? on the simplest benzene surface unless the H‐atoms are substituted by the highly negatively charged F. In this article, we report a type of particularly strong anion–π interactions by investigating the adsorptions of three halide anions, that is, F^?, Cl^?, and Br^?, on the hydrogenated‐graphene flake using the density functional theory. The anion–π interactions on the graphene flake are shown to be unexpectedly strong compared to those on simple aromatic compounds, for example, the F^?‐adsorption energy is as large as 17.5 kcal/mol on a graphene flake (C₈₄H₂₄) and 23.5 kcal/mol in the periodic boundary condition model calculations on a graphene flake C₁₁₃ (the supercell containing a F^? ion and 113 carbon atoms). The unexpectedly large adsorption energies of the halide anions on the graphene flake are ascribed to the effective donor–acceptor interactions between the halide anions and the graphene flake. These findings on the presence of very strong anion–π interactions between halide ions and the graphene flake, which are disclosed for the first time, are hoped to strengthen scientific understanding of the chemical and physical characteristics of the graphene in an electrolyte solution. These favorable interactions of anions with electron‐deficient graphene flakes may be applicable to the design of a new family of neutral anion receptors and detectors. © 2012 Wiley Periodicals, Inc.     

Cucurbit[7]uril Inclusion Complexes with Benzimidazole Derivatives: A Computational Study

Molecular dynamics (MD) simulations were carried out to study the host–guest complexation in aqueous solution between cucurbit[7]uril (CB7) and the neutral and protonated forms of benzimidazole derivatives. Complexation occurs via encapsulation of the hydrophobic part (benzene ring) of the guest within the CB7 hydrophobic cavity, and the interactions of the amine group(s) of the imidazole ring of the guest with the CB7 carbonyl portals. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method is used to estimate the host–guest Gibbs energy of binding. The results indicate that CB7 binds the protonated form more strongly than the neutral one, and that the dominant contribution to the Gibbs energy of complexation for the neutral and protonated guests is associated, respectively, with the host–guest van der Waals and electrostatic interactions. Quantum chemical calculations using dispersion-corrected density functional theory (DFT) are used to calculate the binding affinities and to predict the pK_a values of the free and complexed guests. The calculated pK_a values for the free guests reveal excellent agreement with the experimental values, while for the complexed guests, general trends are obtained.     

Stabilisation of 2,6‐Diarylpyridinium Cation by Through‐Space Polar–π Interactions

The through‐space polar–π interactions between pyridinium ion and the adjacent aromatic rings in 2,6‐diarylpyridines affect the pK_a values. Hammett analysis illustrates that the basicity of pyridines correlates well with the sigma values of the substituents at the para position of the flanking aryl rings.     

氨基甲酸酯型脱氧胆酸分子钳对中性分子的识别性能研究

利用差紫外光谱法考察了新型分子钳1～6对苯胺、对硝基苯胺、对甲氧基苯胺等中性分子的识别性能, 测定了25 ℃下, 在CHCl₃中主客体间的结合常数(K_a)和自由能变化(ΔG⁰). 结果表明, 所有分子钳主体对所考察的客体分子显示良好的识别作用, 主客体间形成1∶1型主客体络合物. 识别作用的主要推动力为多重氢键和π-π重叠等的作用. 讨论了主客体间形状、大小匹配和几何互补及识别模式等因素对识别能力的影响, 并利用核磁共振氢谱与计算机模拟作为辅助手段对实验结果进行了解释.     

Surface plasmon resonance study on binding interactions of multivalent cyclophane hosts with immobilized guests

Guest‐binding affinities of water‐soluble cyclophane heptadecamer (1) and pentamer (2) with immobilized guests such as 1‐pyrenylmethylamine (PMA) and 2‐(1‐ naphthyl)ethylamine (NEA) were investigated by surface plasmon resonance (SPR) measurements. As a typical example, the binding constants (K) for 1 and 2 with the immobilized PMA as a guest were evaluated to be 2.5 × 10⁷ and 2.7 × 10⁶ M^?1, respectively, and were much larger than that of a monocyclic reference cyclophane (K, 2.5 × 10⁴ M^?1). Interestingly, in the complexation of 1 and 2 with the immobilized guests, more favorable association and dissociation rate constant values (k_a and k_d, respectively) were observed in comparison with those for the monocyclic cyclophane, reflecting multivalent effects in macrocycles. The multivalent effects in macrocycles as well as molecular recognition abilities of the cyclophane oligomers were confirmed even when the guest molecules were immobilized on SPR sensor chip surfaces. Copyright © 2009 John Wiley & Sons, Ltd.     

Simultaneous enhancement of phosphorescence and chirality by host–guest recognition of molecular tweezers

A novel type of host–guest recognition systems have been developed on the basis of a Au(III) molecular tweezer receptor and chiral Pt(II) guests. The complementary host–guest motifs display high non-covalent binding affinity (K_a: ～10⁴ L/mol) due to the participation of two-fold intermolecular π–π stacking interactions. Both phosphorescence and chirality signals of the Pt(II) guests strengthen in the resulting host–guest complexes, because of the cooperative rigidifying and shielding effects rendered by the tweezer receptor. Their intensities can be reversibly switched toward pH changes, by taking advantage of the electronic repulsion effect between the protonated form of tweezer receptor and the positive-charged guests in acidic environments. Overall, the current study demonstrates the feasibility to enhance and modulate phosphorescence and chirality signals simultaneously via molecular tweezer-based host–guest recognition.     

Hydrophilic Oligo(lactic acid)s Captured by a Hydrophobic Polyaromatic Cavity in Water

Biologically relevant hydrophilic molecules rarely interact with hydrophobic compounds and surfaces in water owing to effective hydration. Nevertheless, herein we report that the hydrophobic cavity of a polyaromatic capsule, formed through coordination‐driven self‐assembly, can encapsulate hydrophilic oligo(lactic acid)s in water with relatively high binding constants (up to K_a=3×10⁵ m ⁻¹). X‐ray crystallographic and ITC analyses revealed that the unusual host–guest behavior is caused by enthalpic stabilization through multiple CH–π and hydrogen‐bonding interactions. The polyaromatic cavity stabilizes hydrolyzable cyclic di(lactic acid) and captures tetra(lactic acid) preferentially from a mixture of oligo(lactic acid)s even in water.