π‐Conjugated [2]Catenanes Based on Oligothiophenes and Phenanthrolines: Efficient Synthesis and Electronic Properties

Novel π‐conjugated topologies based on oligothiophenes and phenanthroline have been assembled by combining their outstanding electronic and structural benefits with the specific properties of the topological structure. Macrocycles and catenanes are prepared by using an optimized protocol of transition metal‐templated macrocyclization followed by efficient Pd‐catalyzed cross‐coupling reaction steps. By using this method, [2]catenanes comprising two interlocked π‐conjugated macrocycles with different ring sizes have been synthesized. The structures of the [2]catenanes and corresponding macrocycles are confirmed by detailed ¹H NMR spectroscopy and high resolution mass spectrometry. Single crystal X‐ray structural analysis of the quaterthiophene–diyne macrocycle affords important insight into the packing features and intermolecular interaction of the new systems. The fully conjugated interlocked [2]catenanes are fully characterized by spectroscopic and electrochemical measurements.     

Co‐Conformational Distribution of Nanosized [2]Catenanes Determined by Pulse EPR Measurements

The co‐conformational ensembles of three differently sized [2]catenanes were studied by measuring pair correlation functions corresponding to the separation of nitroxide spin labels—one attached to each of the two macrocycles—with the double electron–electron resonance (DEER) experiment. A geometric model for the [2]catenanes was derived that approximates the macrocycles by circles and takes into account the topological constraint. Comparison of the experimental to the theoretically predicted pair correlation functions gives insight into the co‐conformational distribution and the size of the macrocycles. It was found that the macrocycles of the medium‐ and large‐sized catenanes in chloroform are close to fully expanded, while they are partially collapsed in glassy o‐terphenyl. For the small‐sized catenane, moderate interaction between the unsaturated sections of the macrocycles in chloroform is indicated by a slight overrepresentation of short label‐to‐label separations in the pair correlation function.     

Stimuli-Responsive Catenane-Based Catalysts

Rotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli-responsive Cu^I-complexed [2]catenanes as OFF/ON catalysts for the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The encapsulation of the Cu^I ion inside the [2]catenanes inhibits its ability to catalyze the formation of triazoles. In contrast, the controlled opening of the two macrocycles induces the breaking of the mechanical bond, thereby restoring the catalytic activity of the Cu^I ion for the CuAAC reaction. Such OFF/ON catalysts can be involved in signal amplification processes with various potential applications.     

Synthesis of [3]catenanes based on metal-directed self-assembly and pi-donor/pi-acceptor interactions

A metal-directed self-assembly of [3]catenanes in combination with pi-pi interactions was investigated. Ligands based on 4,4'-bipyridinium or 2,7-diazapyrenium were used in conjunction with dioxoaryl cyclophanes (4-6) and trans-PdCl2(CH3CN)2. The [3]catenanes show a dinuclear palladium 46-membered metallomacrocycle interlocked by two pi-complementary dioxoaryl macrocycles. [structure: see text].     

Cucurbit[7]uril: A High‐Affinity Host for Encapsulation of Amino Saccharides and Supramolecular Stabilization of Their α‐Anomers in Water

Cucurbit[7]uril (CB[7]), an uncharged and water‐soluble macrocyclic host, binds protonated amino saccharides (D ‐glucosamine, D ‐galactosamine, D ‐mannosamine and 6‐amino‐6‐deoxy‐D ‐glucose) with excellent affinity (K_a=10³ to 10⁴ M ^?1). The host–guest complexation was confirmed by NMR spectroscopy, isothermal titration calorimetry (ITC), and MALDI‐TOF mass spectral analyses. NMR analyses revealed that the amino saccharides, except D ‐mannosamine, are bound as α‐anomers within the CB[7] cavity. ITC analyses reveal that CB[7] has excellent affinity for binding amino saccharides in water. The maximum affinity was observed for D ‐galactosamine hydrochloride (K_a=1.6×10⁴ M ^?1). Such a strong affinity for any saccharide in water using a synthetic receptor is unprecedented, as is the supramolecular stabilization of an α‐anomer by the host.     

Selective Synthesis of Discrete Mono‐, Interlocked‐, and Borromean Ring Ensembles Based on a π‐Electron‐Deficient Ligand

Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π‐electron‐deficient thiazolo[5,4‐d]thiazole‐derived ligand. We demonstrate that the formation of mono‐rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half‐sandwich Rh^III and Ir^III building blocks. Furthermore, a concentration effect or D‐A stacking interaction between the pyrene guest and the thiazolo[5,4‐d]thiazole‐based ligand promotes a unique and reversible conversion between catenane structures and metalla‐rectangles. The synthetic results are supported by single‐crystal X‐ray diffraction analysis.     

Amide‐Based Oligocatenanes by an Iterative Template Strategy

A new pathway for the supramolecular synthesis of oligocatenanes is developed. It is based on a combination of most suitable macrocyclic structural units, obtained from tert‐butyl‐substituted isophthalic acid and terephthalic acid building blocks. These structural parts guarantee, on the one hand, the solubility of the catenanes and their intermediates, and, on the other hand, the preferred formation of larger ring sizes of the macrocycles to be intertwined. Acting as monotopic and ditopic concave templates, the tetra‐ and octalactam macrocycles were submitted to threading procedures to yield higher‐order catenanes of the amide type. By repetition of the threading steps, it was possible to isolate multiply mechanically connected [n]catenanes up to n=4 composed of various macrocyclic units.     

Surface‐Bound Cucurbit[8]uril Catenanes on Magnetic Nanoparticles Exhibiting Molecular Recognition

We demonstrate the preparation of surface‐bound cucurbit[8]uril (CB[8]) catenanes on silica nanoparticles (NPs), where CB[8] was employed as a tethered supramolecular “handcuff” to selectively capture target guest molecules. In this catenane, CB[8] was threaded onto a methyl viologen (MV²⁺) axle and immobilized onto silica NPs. The formation of CB[8] catenanes on NPs were confirmed by UV/Vis titration experiments and lithographic characterization, demonstrating a high density of CB[8] on the silica NPs surface, 0.56 nm^?2. This CB[8] catenane system exhibits specific molecular recognition towards certain aromatic molecules such as perylene bis(diimide), naphthol and aromatic amino acids, and thus it can act as a nanoscale molecular receptor for target guests. Furthermore, we also demonstrate its use as an efficient and recyclable nano‐platform for peptide separation. By embedding magnetic NPs inside silica NPs, separation could be achieved by simply applying an external magnetic field. Moreover, the peptides captured by the catenanes could be released by reversible single‐electron reduction of MV²⁺. The entire process demonstrated high recoverability.     

Programming A Molecular Relay for Ultrasensitive Biodetection through 129Xe NMR

A supramolecular strategy for detecting specific proteins in complex media by using hyperpolarized ¹²⁹Xe NMR is reported. A cucurbit[6]uril (CB[6])‐based molecular relay was programmed for three sequential equilibrium conditions by designing a two‐faced guest (TFG) that initially binds CB[6] and blocks the CB[6]–Xe interaction. The protein analyte recruits the TFG and frees CB[6] for Xe binding. TFGs containing CB[6]‐ and carbonic anhydrase II (CAII)‐binding domains were synthesized in one or two steps. X‐ray crystallography confirmed TFG binding to Zn²⁺ in the deep CAII active‐site cleft, which precludes simultaneous CB[6] binding. The molecular relay was reprogrammed to detect avidin by using a different TFG. Finally, Xe binding by CB[6] was detected in buffer and in E. coli cultures expressing CAII through ultrasensitive ¹²⁹Xe NMR spectroscopy.     

The Supramolecular Chemistry of Strained Carbon Nanohoops

Since 1996, a growing number of strained macrocycles, comprising only sp²‐ or sp‐hybridized carbon atoms within the ring, have become synthetically accessible, with the [n]cycloparaphenyleneacetylenes ( CPPAs ) and the [n]cycloparaphenylenes ( CPPs ) being the most prominent examples. Now that robust and relatively general synthetic routes toward a diverse range of nanohoop structures have become available, the research focus is beginning to shift towards the exploration of their properties and applications. From a supramolecular chemistry perspective, these macrocycles offer unique opportunities as a result of their near‐perfect circular shape, the unusually high degree of shape‐persistence, and the presence of both convex and concave π‐faces. In this Minireview, we give an overview on the use of strained carbon‐rich nanohoops in host–guest chemistry, the preparation of mechanically interlocked architectures, and crystal engineering.     

Organometallic Borromean Rings and [2]Catenanes Featuring Di-NHC Ligands

We report herein a series of organometallic Borromean rings (BRs) and [2]catenanes prepared from benzobiscarbene ligands. The reaction of dinickel complexes of the benzobiscarbenes 1 a – 1 c with a thiazolothiazole bridged bipyridyl ligand L² led by self-assembly to a series of organometallic BRs. Solvophobic effects played a crucial role in the formation and stability of the interlocked species. The stability of BRs is related to the N-alkyl substituents at the precursors 1 a – 1 c , where longer alkyl substitutes improve stability and inter-ring interactions. Solvophobic effects are also important for the stability of [2]catenanes prepared from 1 a – 1 c and a flexible bipyridyl ligand L³ . In solution, an equilibrium between the [2]catenanes and their macrocyclic building blocks was observed. High proportions of [2]catenanes were obtained in concentrated solutions or polar solvents. The proportion of [2]catenanes in solution could be further enhanced by lengthening of the N-alkyl substitutes.     

Viologen‐Templated Arrays of Cucurbit[7]uril‐Modified Iron‐Oxide Nanoparticles

Magnetic and fluorescent assemblies of iron‐oxide nanoparticles (NPs) were constructed by threading a viologen‐based ditopic ligand, DPV²⁺, into the cavity of cucurbituril (CB[7]) macrocycles adsorbed on the surface of the NPs. Evidence for the formation of 1:2 inclusion complexes that involve DPV²⁺ and two CB[7] macrocycles was first obtained in solution by ¹H NMR and emission spectroscopy. DPV²⁺ was found to induce self‐assembly of nanoparticle arrays (DPV²⁺?CB[7]NPs) by bridging CB[7] molecules on different NPs. The resulting viologen‐crosslinked iron‐oxide nanoparticles exhibited increased saturation magnetization and emission properties. This facile supramolecular approach to NP self‐assembly provides a platform for the synthesis of smart and innovative materials that can achieve a high degree of functionality and complexity and that are needed for a wide range of applications.     

Acylated Triterpene Saponins from Atroxima liberica Stapf

The four new acylated triterpene saponins 1 – 4 , isolated as two pairs of isomers and named libericosides A₁/A₂ and B₁/B₂, one pair of isomers 5 / 6 , the (Z)‐isomer libericoside C₂ ( 5 ) being new, one new sucrose ester, atroximoside ( 7 ), and eight known compounds were isolated from the roots of Atroxima liberica by repeated MPLC and VLC on normal and reversed‐phase silica gel. Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR studies (¹H‐ and ¹³C‐NMR, DEPT, COSY, TOCSY, NOESY, HSQC, and HMBC) and mass spectrometry as 3‐O‐β‐D ‐glucopyranosylpresenegenin 28‐{O‐α‐L ‐arabinopyranosyl‐(1→3)‐O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐4‐O‐[(E)‐3,4‐dimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 1 ) and its (Z)‐isomer 2 , 3‐O‐β‐D ‐glucopyranosylpresenegenin 28‐{O‐α‐L ‐arabinopyranosyl‐(1→4)‐O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)]‐4‐O‐[(E)‐3,4‐dimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 3 ) and its (Z)‐isomer 4 , 3‐O‐β‐D ‐glucopyranosylpresenegenin 28‐{O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[6‐O‐acetyl‐β‐D ‐glucopyranosyl‐(1→3)]‐4‐O‐[(Z)‐3,4‐dimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 5 ), and 3‐O‐[(Z)‐feruloyl]‐β‐D ‐fructofuranosyl α‐D ‐glucopyranoside ( 7 ). Compounds 1 – 6 and the known saponins 8 / 9 were evaluated against the human colon cancer cells HCT 116 and HT‐29 and showed moderate to weak cytotoxicity.     

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene,as evaluated by varied 1H‐NMR approaches

This study focused on the use of NMR techniques as a tool for the investigation of complex formation between proparacaine and cyclodextrins (CDs) or p‐sulfonic acid calix[6]arene. The pH dependence of the complexation of proparacaine with β‐CD and p‐sulfonic acid calix[6]arene was studied and binding constants were determined by ¹H NMR spectroscopy [diffusion‐ordered spectroscopy (DOSY)] for the charged and uncharged forms of the local anesthetic in β‐CD and p‐sulfonic acid calix[6]arene. The stoichiometries of the complexes was determined and rotating frame Overhauser enhancement spectroscopy (ROESY) 1D experiments revealed details of the molecular insertion of proparacaine into the β‐CD and p‐sulfonic acid calix[6]arene cavities. The results unambiguously demonstrate that pH is an important factor for the development of supramolecular architectures based on β‐CD and p‐sulfonic acid calix[6]arene as the host molecules. Such host–guest complexes were investigated in view of their potential use as new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of proparacaine in anesthesia procedures. Copyright © 2009 John Wiley & Sons, Ltd.     

Asararenes—A Family of Large Aromatic Macrocycles

We announce the establishment of a new family of macrocycles—the asararenes, which are based on para‐methylene linked “asarol methyl ether” (1,2,4,5‐tetramethoxybenzene) units. Macrocycles with 6–12 aromatic units have been synthesized and isolated in a single step from asarol methyl ether and paraformaldehyde. Even larger rings, with up to 15 asarol methyl ether units, have been observed by high‐resolution mass spectrometry. Single‐crystal X‐ray structures of asar[6]‐, asar[7]‐, asar[8]‐, asar[9]‐, asar[10]‐ and asar[11]arene highlight the diverse structural features of this family of macrocycles. While the cavities of the asar[6–8]arene macrocycles are mostly filled with methoxyl groups, the asar[9]‐ and asar[10]arene rings contain accessible cavities and self‐assemble into infinite channels filled with solvent molecules in the solid state. These solid‐state structures highlight the potential of this family of macrocycles for a wide range of potential applications.     

Detailed Investigation of the Immunodominant Role of O‐Antigen Stoichiometric O‐Acetylation as Revealed by Chemical Synthesis,Immunochemistry, Solution Conformation and STD‐NMR Spectroscopy for Shigella flexneri 3a

Shigella flexneri 3a causes bacillary dysentery. Its O‐antigen has the {2)‐[α‐d ‐Glcp‐(1→3)]‐α‐l ‐Rhap‐(1→2)‐α‐l ‐Rhap‐(1→3)‐[Ac→2]‐α‐l ‐Rhap‐(1→3)‐[Ac→6]_{≈40 %}‐β‐d ‐GlcpNAc‐(1→} ([(E)AB_AcC_AcD]) repeating unit, and the non‐O‐acetylated equivalent defines S. flexneri X. Propyl hepta‐, octa‐, and decasaccharides sharing the (E′)A′B_AcCD(E)A sequence, and their non‐O‐acetylated analogues were synthesized from a fully protected B_AcCD(E)A allyl glycoside. The stepwise introduction of orthogonally protected mono‐ and disaccharide imidate donors was followed by a two‐step deprotection process. Monoclonal antibody binding to twenty‐six S. flexneri types 3a and X di‐ to decasaccharides was studied by an inhibition enzyme‐linked immunosorbent assay (ELISA) and STD‐NMR spectroscopy. Epitope mapping revealed that the 2_C‐acetate dominated the recognition by monoclonal IgG and IgM antibodies and that the B_AcCD segment was essential for binding. The glucosyl side chain contributed to a lesser extent, albeit increasingly with the chain length. Moreover, tr‐NOESY analysis also showed interaction but did not reveal any meaningful conformational change upon antibody binding.     

New single isomer negatively charged β‐cyclodextrin derivatives as chiral selectors in capillary electrophoresis

To improve resolution power of chiral selector and enantiomeric peak efficiency in CE, single isomer negatively charged β‐CD derivatives, mono(6‐deoxy‐6‐sulfoethylthio)‐β‐CD (SET‐β‐CD) bearing one negative charge and mono[6‐deoxy‐6‐(6‐sulfooxy‐5,5‐bis‐sulfooxymethyl)hexylthio]‐β‐CD (SMHT‐β‐CD) carrying three negative charges, were synthesized. The structure of these two β‐CD derivatives was confirmed by ¹H NMR and MS. SET‐β‐CD and SMHT‐β‐CD successfully resolved the enantiomers of several basic model compounds. SMHT‐β‐CD provided for a significantly greater enantioseparation than SET‐β‐CD at lower concentrations. This appears to be due to the higher binding affinity of SMHT‐β‐CD to the model compounds and the wider separation window resulting from an increased countercurrent mobility of the selector. Overall, the new chiral selectors provided enantioseparations with high peak efficiency while avoiding peak distortion due to polydispersive and electrodispersive effects. The information obtained from an apparent binding constant study suggested that the enantioseparation of the model compounds followed the predictions of charged resolving agent migration model and that the observed degree of enantioseparation difference were due to the magnitude of differences in both enantiomer‐chiral selector binding affinities (ΔK) and the mobilities of the complexed enantiomers (Δμ_c).     

Nondegenerate pi-donor/pi-acceptor [2]catenanes containing proton-ionizable 1H-1,2,4-triazole subunits: synthesis and spontaneous resolution

Chirality can hold the key to inducing directionality of motion in components of molecular devices. With this idea in mind, we describe here 1) the template-directed synthesis of two [2]catenanes wherein cyclobis(paraquat-p-phenylene) is interlocked with polyether macrocycles containing, in addition to one 3,5-bis(oxymethylene)-1H-1,2,4-triazole unit, either one 1,4-dioxybenzene or one 1,5-dioxynaphthalene ring system. We also report 2) the full characterization of both [2]catenanes by fast atom bombardment mass spectrometry (FABMS), X-ray crystallography, and dynamic (1)H NMR spectroscopy. We reveal 3) the fact that the [2]catenanes not only exist, both in the solution-state and in the solid-state, as strictly one of the two possible translational isomers, but that they also exhibit spontaneous resolution on crystallization leading to formation of homochiral crystals, as indicated by X-ray crystallography and circular dichroism (CD) experiments. Finally, we comment 4) on the chances of switching these catenanes chemically.     

Building [2]Catenanes around a Tris(diimine)ruthenium(2+) ([Ru(diimine)3]2+) Complex Core Used as Template

In the course of the last two decades, the use of transition metals as templates for constructing catenanes has almost exclusively been restricted to tetrahedral copper(I). The present work is dealing with an octahedral metal, ruthenium(II), coordinated to three bidentate chelates. Incorporation of two chelates (1,10‐phenanthroline) in a ring allows to prepare a C₂‐symmetric ruthenium complex, the two chelates being disposed cis to one another (see 14 ²⁺ and 16 ²⁺ in Scheme 5 and 6, resp.). The ring is large enough to accomodate a third chelate, thus allowing the metal‐directed threading of a long fragment containing the third chelate (2,2′‐bipyridine derivative; see 23 ²⁺ and 24 ²⁺ in Scheme 8). The last step consists of a ring‐closing metathesis reaction with two terminal olefins. The two ruthenium(II)‐complexed catenanes 25 ²⁺ and 26 ²⁺ were prepared by using this strategy, each containing a 42‐membered ring interlocked to a larger macrocycle (50‐ or 63‐membered ring) incorporating the two 1,10‐phenanthroline chelates. It is expected that these catenanes can be set in motion under light‐irradiation, thus behaving as photochemically driven molecular machines.     

New Acylated Presenegenin Saponins from Two Species of Muraltia

Six new acylated bisdesmosidic triterpene glycosides 1 – 6 were isolated from the roots of Muraltia heisteria (L.) DC., as three inseparable mixtures 1 / 2, 3 / 4 , and 5 / 6 of the (E)‐ and (Z)‐3,4,5‐trimethoxycinnamoyl derivatives. The compound pair 1 / 2 along with four known saponins were also isolated from the roots of Muraltia satureioides DC. Their structures were elucidated mainly by spectroscopic experiments including 2D‐NMR techniques as 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐{O‐β‐D ‐apiofuranosyl‐(1→3)‐O‐[β‐D ‐xylopyranosyl‐(1→4)]‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[6‐O‐acetyl‐β‐D ‐galactopyranosyl‐(1→3)]‐4‐O‐[(E)‐3,4,5‐trimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 1 ) and its (Z)‐isomer 2 , 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐{O‐6‐O‐acetyl‐β‐D ‐galactopyranosyl‐(1→3)‐O‐[3‐O‐acetyl‐α‐L ‐rhamnopyranosyl‐(1→2)]‐4‐O‐[(E)‐3,4,5‐trimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 3 ) and its (Z)‐isomer 4 , and 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐{O‐3‐O‐acetyl‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[β‐D ‐xylopyranosyl‐(1→3)]‐4‐O‐[(E)‐3,4,5‐trimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 5 ) and its (Z)‐isomer 6 , respectively.