Oxa-TriQuinoline: A New Entry to Aza-Oxa-Crown Architectures.

A new 15-membered-macrocyclic molecular entity, oxa-TriQuinoline (o-TQ), was designed and synthesized. In o-TQ, three oxygen atoms were joined onto three quinoline units at the 2- and 8-positions in a head-to-tail fashion by three-fold SN Ar reactions, giving rise to the characteristic N3 O3 aza-oxa-crown architecture. o-TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π-π and CH-π interactions. In the presence of the CuI cation, the non-emissive o-TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o-TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem-difluorinated terminus.

Synthesis of Novel Crown Ether-Squaramides and Their Application as Phase-Transfer Catalysts.

This work presents the synthesis of six new phase-transfer organocatalysts in which the squaramide unit is directly linked to the nitrogen atom of an aza-crown ether. Four chiral skeletons, namely hydroquinine, quinine, cinchonine (cinchonas), and α-d-glucopyranoside were responsible for the asymmetric construction of an all-carbon quaternary stereogenic center in α-alkylation and Michael addition reactions of malonic esters. We investigated the effects of these different chiral units and that of crown ethers with different sizes on catalytic activity and enantioselectivity. During extensive parameter investigations, both conventional and emerging green solvents were screened, providing valuable α,α-disubstituted malonic ester derivatives with excellent yields (up to 98%).

Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides.

The first highly enantioselective arylogous Michael reaction (AMR) of 3-unsubstituted phthalides has been described. This phase-transfer methodology, which uses catalytic amounts of KOH/18-crown-6 catalyst in mesitylene in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3-monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3-unsubstituted derivatives and diverse α,ß-unsaturated carbonyl compounds. The reaction also applies to unactivated 3-alkyl phthalides to afford 3,3-dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant.

[2]Pseudorotaxane-Based Supramolecular Optical Indicator for the Visual Detection of Cellular Cyanide Excretion.

Cyanide is extremely hazardous to living organisms and the environment. Owing to its wide range of applications and high toxicity, the development of functional materials for cyanide detection and sensing is highly desirable. Host-guest complexation between bis(p-phenylene)-34-crown-10 H and N-methylacridinium salt G remarkably decreases the detection limit for cyanide anions compared with that of the guest itself. The [2]pseudorotaxane selectively recognizes the cyanide anion with high optical sensitivity as a result of the nucleophilic addition of the cyanide anion at the 9-position of G. The host-guest complexation is further incorporated into supramolecular materials for the visual detection of cyanide anions, especially the detection of cellular cyanide excretion with a detection limit of 0.6 µm. This supramolecular method provides an extremely distinct strategy for the visual detection of cyanide anions.

Donor-Acceptor [2]- and [3]Catenanes Assembled from Versatile Pre-Organized Cp*Rh/Ir-Directed Pseudorotaxane Tectons.

A stepwise self-assembly protocol has been used to synthesize [2]- and [3]catenanes. Firstly, binuclear Cp*Rh/Ir-directed (Cp*=pentamethylcyclopentadienyl) pseudorotaxanes were prepared through self-assembly, driven by donor-acceptor interactions between electron-deficient naphthalenediimide (NDI) units and an electron-rich crown ether. Subsequently, the pre-organized pseudorotaxanes were applied as tectons for self-assembly of [2]- and [3]catenanes by combination with very simple linkers. The structures of the catenanes were confirmed by NMR spectroscopy, ESI mass spectrometry, single-crystal X-ray diffraction analysis, and elemental analysis.

Na+ Selective Fluorescent Tools Based on Fluorescence Intensity Enhancements, Lifetime Changes, and on a Ratiometric Response.

Over the years, we developed highly selective fluorescent probes for K+ in water, which show K+ -induced fluorescence intensity enhancements, lifetime changes, or a ratiometric behavior at two emission wavelengths (cf. Scheme 1, K1-K4). In this paper, we introduce selective fluorescent probes for Na+ in water, which also show Na+ induced signal changes, which are analyzed by diverse fluorescence techniques. Initially, we synthesized the fluorescent probes 2, 4, 5, 6 and 10 for a fluorescence analysis by intensity enhancements at one wavelength by varying the Na+ responsive ionophore unit and the fluorophore moiety to adjust different Kd values for an intra- or extracellular Na+ analysis. Thus, we found that 2, 4 and 5 are Na+ selective fluorescent tools, which are able to measure physiologically important Na+ levels at wavelengths higher than 500 nm. Secondly, we developed the fluorescent probes 7 and 8 to analyze precise Na+ levels by fluorescence lifetime changes. Herein, only 8 (Kd =106 mm) is a capable fluorescent tool to measure Na+ levels in blood samples by lifetime changes. Finally, the fluorescent probe 9 was designed to show a Na+ induced ratiometric fluorescence behavior at two emission wavelengths. As desired, 9 (Kd =78 mm) showed a ratiometric fluorescence response towards Na+ ions and is a suitable tool to measure physiologically relevant Na+ levels by the intensity change of two emission wavelengths at 404 nm and 492 nm.

Supramolecular Gel Based on Crown-Ether-Appended Dynamic Covalent Macrocycles.

A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.

One-Step Assembly of Visible and Near-Infrared Emitting Metallacrown Dimers Using a Bifunctional Linker.

A family of dimeric LnIII [12-MCGa(III)N(shi) -4] metallacrowns (MCs) (LnIII =Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) was synthesized using the isophthalate group (ip2- ) as a linker. The [LnGa4 ]2 complexes exhibit remarkable photophysical properties, with large molar absorptivities of ≈4×104 m-1 cm-1 , high quantum yields and long luminescence lifetimes with values of (i) 31.2(2)% and 1.410(1) ms, respectively for the visible-emitting [TbGa4 ]2 complex and (ii) 2.43(6)% and 30.5(1) µs for the near-infrared (NIR) emitting [YbGa4 ]2 in the solid state. The NIR emission was obtained not only from Yb, Nd, and Er complexes but also from the less frequently observed emitters such as Pr and Ho. In addition, emission in both visible and NIR domains could be detected for Dy and Sm MCs. ESI-MS and UV/Vis data revealed that the complexes are highly stable in dimethylsulfoxide (DMSO) solution with the 1 H- and COSY-NMR spectra of the diamagnetic [YGa4 ]2 analogue providing evidence for long-term solution stability. This new approach allows one to construct a basis for highly luminescent MCs that may be further modified to be adapted for applications such as optical imaging.

Ion Selectivity in Nonpolymeric Thermosensitive Systems Induced by Water-Attenuated Supramolecular Recognition.

The chemistry of aqueous salt solutions is rich with ambiguities, especially in stimuli-responsive supramolecular systems. Rational use of ion specificity to design supramolecular responsive materials, however, remains a challenging task. In this work, a low-molecular-weight supramolecular system was developed that was used to reveal the underlying systematic relationship between ions, water, and solutes. By utilizing these water-attenuated supramolecular forces (with Ka only ca. 30 m-1 ), an alternative concept for fabricating an aqueous responsive system in ionic medium was demonstrated. This work not only provides mechanistic insight into the underdeveloped role of topology in ion specificity upon noncharged polar surfaces, but also demonstrates the feasibility of utilizing weak supramolecular approaches to control the thermoresponsiveness.

A Ratiometric Fluorescent Probe for K+ in Water Based on a Phenylaza-18-Crown-6 Lariat Ether.

This work presents two molecular fluorescent probes 1 and 2 for the selective determination of physiologically relevant K+ levels in water based on a highly K+ /Na+ selective building block, the o-(2-methoxyethoxy)phenylaza-18-crown-6 lariat ether unit. Fluorescent probe 1 showed a high K+ -induced fluorescence enhancement (FE) by a factor of 7.7 of the anthracenic emission and a dissociation constant (Kd ) value of 38 mm in water. Further, for 2+K+ , we observed a dual emission behavior at 405 and 505 nm. K+ increases the fluorescence intensity of 2 at 405 nm by a factor of approximately 4.6 and K+ decreases the fluorescence intensity at 505 nm by a factor of about 4.8. Fluorescent probe 2+K+ exhibited a Kd value of approximately 8 mm in Na+ -free solutions and in combined K+ /Na+ solution a similar Kd value of about 9 mm was found, reflecting the high K+ /Na+ selectivity of 2 in water. Therefore, 2 is a promising fluorescent tool to measure ratiometrically and selectively physiologically relevant K+ levels.

Distinguishing Two Ammonium and Triazolium Sites of Interaction in a Three-Station [2]Rotaxane Molecular Shuttle.

This paper reports on the synthesis of a tri-stable [2]rotaxane molecular shuttle, in which the motion of the macrocycle is triggered by either selective protonation/deprotonation or specific carbamoylation/decarbamoylation of an alkylbenzylamine. The threaded axle is surrounded by a dibenzo[24]crown[8] (DB24C8) macrocycle and contains three sites of different binding affinities towards the macrocycle. An N-methyltriazolium moiety acts as a molecular station that has weak affinity for the DB24C8 macrocycle and is located in the centre of the molecular axle. Two other molecular stations, arylammonium and alkylbenzylammonium moieties, sit on either side of the triazolium moiety along the molecular axle and have stronger affinities for the DB24C8 macrocycle. These two ammonium moieties are covalently linked to two different stopper groups at each extremity of the thread: a tert-butylphenyl group and a substituted DB24C8 unit. Owing to steric hindrance, the former does not allow any π-π stacking interactions with the encircling DB24C8 macrocycle, whereas the latter residue does; therefore, this allows the discrimination of the two ammonium stations by the surrounding DB24C8 macrocycle in the fully protonated state. In the deprotonated state, the contrasting reactivity of the amine functional groups, as either a base or a nucleophile, allows for selective reactions that trigger the controlled shuttling of the macrocycle around the three molecular stations.

Design of Na+ -Selective Fluorescent Probes: A Systematic Study of the Na+ -Complex Stability and the Na+ /K+ Selectivity in Acetonitrile and Water.

There is a tremendous demand for highly Na+ -selective fluoroionophores to monitor the top analyte Na+ in life science. Here, we report a systematic route to develop highly Na+ /K+ selective fluorescent probes. Thus, we synthesized a set of fluoroionophores 1, 3, 4, 5, 8 and 9 (see Scheme ) to investigate the Na+ /K+ selectivity and Na+ - complex stability in CH3 CN and H2 O. These Na+ -probes bear different 15-crown-5 moieties to bind Na+ stronger than K+ . In the set of the diethylaminocoumarin-substituted fluoroionophores 1-5, the following trend of fluorescence quenching 1>3>2>4>5 in CH3 CN was observed. Therefore, the flexibility of the aza-15-crown-5 moieties in 1-4 determines the conjugation of the nitrogen lone pair with the aromatic ring. As a consequence, 1 showed in CH3 CN the highest Na+ -induced fluorescence enhancement (FE) by a factor of 46.5 and a weaker K+ induced FE of 3.7. The Na+ -complex stability of 1-4 in CH3 CN is enhanced in the following order of 2>4>3>1, assuming that the O-atom of the methoxy group in the ortho-position, as shown in 2, strengthened the Na+ -complex formation. Furthermore, we found for the N-(o-methoxyphenyl)aza-15-crown-5 substituted fluoroionophores 2, 8 and 9 in H2 O, an enhanced Na+ -complex stability in the following order 8>2>9 and an increased Na+ /K+ selectivity in the reverse order 9>2>8. Notably, the Na+ -induced FE of 8 (FEF=10.9), 2 (FEF=5.0) and 9 (FEF=2.0) showed a similar trend associated with a decreased K+ -induced FE [8 (FEF=2.7)>2 (FEF=1.5)>9 (FEF=1.1)]. Here, the Na+ -complex stability and Na+ /K+ selectivity is also influenced by the fluorophore moiety. Thus, fluorescent probe 8 (Kd =48 mm) allows high-contrast, sensitive, and selective Na+ measurements over extracellular K+ levels. A higher Na+ /K+ selectivity showed fluorescent probe 9, but also a higher Kd value of 223 mm. Therefore, 9 is a suitable tool to measure Na+ concentrations up to 300 mm at a fluorescence emission of 614 nm.

A Highly Effective Strategy for Encapsulating Potassium Cations in Small Crown Ether Rings on a Dinuclear Palladium Complex.

The potential of 15-crown-5 ethers to link large cations, such as potassium, is limited by the quasi-parallel arrangement of two oxygen donor moieties upon appropriate orientation of the corresponding ether-ring-containing molecules. Substrates bearing the two crown ethers that are capable of achieving such coordination are hitherto unknown. The synthesis and isolation of a tailor-made dinuclear palladacycle bearing 15-crown-5 ether rings on the metallated phenyls offers such a possibility, providing the adequate environment for the formation of the sandwiched [K(metallacycle-15-crown-5)2 ] moiety. This synthetic strategy also culminates in the isolation of the first palladacycle able to entrap a potassium cation through bonding to two 15-crown-5 ether rings in a single molecule.

Cooperative Noncovalent Interactions Induce Ion Pair Separation in Diphenylsilanides.

This crystallographic and computational study describes an unusual potassium silanide structure. A contact ion pair is expected in the solid state between potassium and silicon, yet the potassium cation binds an aromatic ring and the anionic silanide interacts with CH bonds on neighboring crown ether molecules. These structure-bonding phenomena are attributed to strong soft-soft interactions.

Chiral Discrimination through 1 H†NMR and Luminescence Spectroscopy: Dynamic Processes and Solid Strip for Chiral Recognition.

The appropriate choice of the host molecules with well-defined optical activity (S-H/R-H) helps in the differentiation between two secondary ammonium ion-derivative guest molecules with different optical activities (R-G/S-G) based on the fluorescence resonance energy transfer (FRET)-based luminescence responses. Crown ether-based host molecules with opposite chiral configurations (R-H, S-H) have been derived from 1,1'-bi-2-naphthol (BINOL) derivatives that have axially chiral biaryl centers. These chiral crown ethers form host-guest complexes (i.e., [2]pseudorotaxanes) with chiral secondary ammonium ion derivatives (R-G, S-G). NMR spectroscopic studies show that the complexes are in a dynamic equilibrium in solution. Results of the 1 H NMR and fluorescence spectroscopic studies indicate a head-on orientation of the host and guest in the [2]pseudorotaxanes. The difference in the efficiency in the FRET-based responses between anthracene and the BINOL derivatives allow efficient chiral discrimination of the guests. Isothermal titration calorimetry and NMR investigations reveal that inclusion complexes between hosts and guests of the same chirality (R-H⋅R-G, S-H⋅S-G) are more stable relative to those of opposite chirality (R-H⋅S-G, S-H⋅R-G). However, FRET-based energy-transfer efficiency is higher for R-H⋅S-G and S-H⋅R-G complexes. NMR spectroscopic studies show that the relative orientation of the guest in the host cavity is significantly different when the host binds a guest of the same or opposite chirality; furthermore, the latter is more favorable for FRET, thus enabling discrimination between enantiomers. Interestingly, chiral discrimination of guest ions could also be achieved by using silica surfaces modified with chiral host molecules.

Crown Ether Complexes of Alkali-Metal Chlorides from SO2.

The structures of alkali-metal chloride SO2 solvates (Li-Cs) in conjunction with 12-crown-4 or 1,2-disila-12-crown-4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2-disila-12-crown-4)(SO2 Cl)] (1) and [Li(12-crown-4)Cl]⋅4 SO2 (2). However, 1,2-disila-12-crown-4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich-type complexes. As a result, 12-crown-4 reacts exclusively with the heavier alkali-metal chlorides NaCl, KCl and RbCl. Compounds [Na(12-crown-4)2 ]Cl⋅4 SO2 (3) and [M(12-crown-4)2 (SO2 )]Cl⋅4 SO2 (4: M=K; 5: M=Rb) all showed S-coordination to the chloride ions through four SO2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non-bridging O,O'-coordination mode of SO2 . Unexpectedly, the disila-crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO2 -solvated alkali-metal chlorides [MCl⋅3 SO2 ] (6: M=Rb; 7: M=Cs), which incorporate bridging µ-O,O'-coordinating moieties and the unprecedented side-on O,O'-coordination mode. All compounds were characterised by single-crystal X-ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO2 at ambient temperature was revealed by IR spectroscopy of the neat compounds.

Polymer Segments at the Folding Limit: Raman Scattering for the Diglyme Benchmark.

Methyl-capped polyethers model flexible polar polymer chains. Their intrinsic all-trans conformational preference gives way to folded conformations if the chain is sufficiently long. We find by Raman cryospectroscopy in the gas phase and quantum chemical calculations that diglyme still prefers the stretched state, although folded variants come very close in energy. Three-body dispersion correction or higher-order electron correlation is important to match experiments, despite the polar character of C-O bonds. This turns oligoglymes into challenging benchmark systems for a balanced description of intra-chain torsion and inter-segment van der Waals attraction.

Benchmark Ditopic Binding of Cl- and Cs+ by the Macrocycle Hexacyclen.

The ditopic binding of organic and inorganic anions and cations constitutes a distinct feature of polyazamacrocycles that underlies their action as intermediate docking and exchange ionophoric sites for tailored supramolecular synthesis and sensors. This work investigates the Cl- and Cs+ complexes formed by hexacyclen (1,4,7,10,13,16-hexaazacyclooctadecane, ha18c6), a benchmark building block of ion-pair polyamine receptors. IR action spectroscopy is employed to characterize the anionic and cationic complexes under controlled environmental conditions in an ion trap. This allows for accurate modeling of the isolated complexes with quantum chemical computations. A comparison of the experimental and computational spectra serves to assess the low-energy conformers dominantly populated at room temperature, which comprise, in both cases, three structures of Cs , C2 , and C3v symmetry with relative energies within about 5 kJ mol-1 . The ion-pair complex Cl- -ha18c6-Cs+ is predicted to host the cation and anion on opposite sides of the macrocycle in a C3v conformation that does not correlate with the lowest energy structures of the binary complexes. This indicates that the formation of the ion-pair complex in its most stable conformation demands a rearrangement of the hexacyclen ring structure upon the incorporation of the counterion.

Catalytic Direct-type 1,4-Addition Reactions of Alkylazaarenes.

1,4-addition reactions of alkylazaarenes catalyzed by strong Brønsted bases have been developed for the first time. The desired reactions with α,ß-unsaturated amides proceeded under mild reaction conditions to give the 1,4-adducts in high yields. Both ortho- and para-substituted azaarenes afforded the desired adducts in high yields. Regioselective reactions of di- or trimethylpyridine were found to be possible depending on the acidity of the α-hydrogen atoms. Furthermore, a candidate of allosteric protein kinase modulators was synthesized in two steps. An asymmetric variant of this reaction was also found to be feasible.

Active Esters as Pseudostoppers for Slippage Synthesis of [2]Pseudorotaxane Building Blocks: A Straightforward Route to Multi-Interlocked Molecular Machines.

The efficient synthesis and very easy isolation of dibenzo[24]crown-8-based [2]pseudorotaxane building blocks that contain an active ester motif at the extremity of the encircled molecular axle and an ammonium moiety as a template for the dibenzo[24]crown-8 is reported. The active ester acts both as a semistopper for the [2]pseudorotaxane species and as an extensible extremity. Among the various investigated active ester moieties, those that allow for the slippage process are given particular focus because this strategy produces fewer side products. Extension of the selected N-hydroxysuccinimide ester based pseudorotaxane building block by using either a mono- or a diamino compound, both containing a triazolium moiety, is also described. These provide a pH-dependent two-station [2]rotaxane molecular machine and a palindromic [3]rotaxane molecular machine, respectively. Molecular machinery on both interlocked compounds through variation of pH was studied and characterized by means of NMR spectroscopy.