Macrocyclic Dinuclear Palladium Complex as a Novel Doubly Threaded [3]Rotaxane Scaffold and Its Application as a Rotaxane Cross‐Linker

A dinuclear Pd^II complex possessing a cyclic ligand was developed as a novel doubly threaded [3]rotaxane scaffold and applied as a rotaxane cross‐linker reagent. The dinuclear complex (PdMC)₂ was prepared by one‐step macrocyclization followed by the double palladation reaction. ¹H NMR analysis and UV/Vis measurements revealed the formation of a doubly threaded pseudo[3]rotaxane by the complexation of (PdMC)₂ with 2 equivalents of 2,6‐disubstituted pyridine 3 through double metal coordination. The treatment of (PdMC)₂ with 2 equivalents of 4‐vinylpyridine (VP) afforded a doubly threaded [3]rotaxane cross‐linker (PdMC‐VP)₂ . Radical co‐polymerization of VP and t‐butylstyrene in the presence of (PdMC‐VP)₂ afforded a stable rotaxane cross‐linked polymer (RCP). An elastic RCP was also prepared by using n‐butyl acrylate as a monomer. The obtained RCPs exhibited higher swelling ability and higher mechanical toughness compared with the corresponding covalent cross‐linked polymers.     

Guest Recognition Control Accompanied by Stepwise Gate Closing and Opening of a Macrocyclic Metallohost

Host–guest binding behavior of macrocyclic hosts is significantly influenced by the shapes and sizes of the hosts. In particular, closing/opening the apertures of the hosts controls the guest uptake/release. A post-metalation modification method was used to achieve the open/close conversions. The starting open complex, [LCo₂(pip)₄](OTf)₂, was efficiently converted to the closed complex, [LCo₂(hda)₂](OTf)₂, which has a doubly bridged structure. The conversion of this closed complex to the open complex [LCo₂(hda)₂(OAc)]⁺ was too slow to be completed, but this gate-opening was dramatically accelerated by the addition of Na⁺. The Na⁺ binding was also significantly enhanced by the gate-opening, that is, conversion of [LCo₂(hda)₂]²⁺ to [LCo₂(hda)₂(OAc)]⁺.     

Sensing Behavior of Fluorescent Cyclodextrin/Peptide Hybrids Bearing a Macrocyclic Metal Complex

Two kinds of cyclodextrin/peptide (CD/peptide) hybrids bearing Zn^II‐cyclen or cyclen, dansyl and β‐cyclodextrin (β‐CD) units have been synthesized as chemosensors for organic anionic molecules. Zn^II‐cyclen serves as a ligand site and β‐CD is a receptor site for guest molecules, while the dansyl unit acts as a fluorescent probe. Examination of the fluorescence behaviors of these CD/peptides suggest that the hybrid containing Zn²⁺ has larger binding constants with respect to anionic molecules than that without Zn²⁺.

     

Templated synthesis of a rotaxane with a [Ru(diimine)3]2+ core

A rotaxane containing a ruthenium bisphenanthroline complex, acting as an axis, and a macrocycle incorporating a 2,2'-bipyridine (bpy) unit, threaded by the axis, has been synthesized. The bisphenanthroline ligand is such that its ruthenium(II) complexes possess a clearly identified axis, making such compounds ideal components of rotaxanes constructed around an octahedral ruthenium(II) center, which serves as a template. The ring is threaded by the axial ruthenium(II) precursor complex, to afford the corresponding pseudorotaxane in moderate yield. The X-ray structure analysis of this compound reveals the threaded nature of the complex. The length of the threaded ring (35 atoms in the periphery) is too short to allow easy threading of the axis through the macrocycle. As a consequence, an isomer is also obtained for which the axial ruthenium complex is attached in an exo fashion. (1)H NMR studies have been carried out, which reveal various conformational equilibria for the pseudorotaxane. Light-induced decoordination of the bpy-containing cyclic fragment was shown to be quantitative and to lead to the free ring and the axial ruthenium(II) complex, regardless of the starting compound (pseudorotaxane or exo isomer). Finally, the real rotaxane could be prepared, although it could not be separated from its exo isomer.     

Highly Selective Binding and Inhibition of Pyr-His-Pro-NH2 (TRH) Function using a Polypyridinyl Macrocyclic Receptor with an Amphiphilic Cavity

Macrocycle, cyclo[4] [(1,3-(4,6)-dimethylbezene)[4](2,6-(3,5)-dimethylpyridine ( B4P4 ), shows highly selective binding affinity with protirelin (Pyr-His-Pro-NH₂; TRH) among the tested 26 drug or drug adductive substrates. The stable complexation in a 1:1 manner was fully characterized in solution, gas phase, and solid state study. Furthermore, B4P4 acts as an efficient TRH inhibitor even at [macrocycle]:[drug] <1:300, both in membrane transport and cellar incubation. The current work provides an unprecedented strategy for macrocycles to be efficiently used in drug target therapy.     

A Tray‐Shaped,PdII‐Clipped Au3 Complex as a Scaffold for the Modular Assembly of [3×n] Au Ion Clusters

A tray‐shaped Pd^II₃Au^I₃ complex ( 1 ) is prepared from 3,5‐bis(3‐pyridyl)pyrazole by means of tricyclization with Au^I followed by Pd^II clipping. Tray 1 is an efficient scaffold for the modular assembly of [3×n] Au^I clusters. Treatment of 1 with the Au^I₃ tricyclic guest 2 in H₂O/CH₃CN (7:3) or H₂O results in the selective formation of a [3×2] cluster ( 1 ? 2 ) or a [3×3] cluster ( 1 ? 2 ? 1 ), respectively. Upon subsequent addition of Ag^I ions, these complexes are converted to an unprecedented Au₃–Au₃–Ag–Au₃–Au₃ metal ion cluster.     

Photophysical Properties and Conformational Effects on the Circular Dichroism of an Azobenzene–Cyclodextrin [1]Rotaxane and Its Molecular Components

The photophysical properties of a multicomponent [1]rotaxane bearing a β‐cyclodextrin ring covalently connected to an axle comprising an azobenzene photoisomerisable moiety and a naphthalimide‐type fluorescent stopper are investigated by a combined experimental and computational study. The absorption and fluorescence spectra, and particularly the induced circular dichroism (ICD) signal, are determined. The latter shows a sign relation that cannot be rationalised in terms of the simple general rules commonly employed to analyse the ICD spectra of achiral guests encircled by chiral hosts. To assist the interpretation of experimental results, DFT and time‐dependent (TD) DFT calculations are performed to explore the availability of low‐energy conformations and to model their spectroscopic response. Molecular dynamics simulations performed in water show the interconversion of a number of conformers, the contribution of which to the ICD signal is in agreement with the observation.     

A Cucurbit[8]uril 2:2 Complex with a Negative pKa Shift

A viologen derivative carrying a benzimidazole group ( V-P-I ²⁺; viologen–phenylene–imidazole V-P-I ) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK_a, by more than 1 pH unit, contrasting with the positive pK_a shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation. The addition of CB[8] to a solution containing V-P- I ³⁺ indeed released protons as monitored by pH-metry and visualized by a coloured indicator. This property was used to induce a host/guest swapping, accompanied by a proton transfer, between V-P-I ³⁺ ⋅ CB[7] and a CB[8] complex of 1-methyl-4-(4-pyridyl)pyridinium. The origin of this negative pK_a shift is proposed to stand in an ideal charge state, and in the position of the two pH-responsive fragments inside the two CB[8] which, alike residues engulfed in proteins, favour the deprotonated form of the guest molecules. Such proton release triggered by a recognition event is reminiscent of several biological processes and may open new avenues toward bioinspired enzyme mimics catalyzing proton transfer or chemical reactions.     

Enhanced and Heteromolecular Guest Encapsulation in Nonporous Crystals of a Perfluorinated Triketonato Dinuclear Copper Complex

The flexible host framework of a perfluorinated mononuclear copper complex, [Cu(L¹)₂] ( 1 , HL¹=3-hydroxy-1,3-bis(pentafluorophenyl)-2-propen-1-one), with a CuO₄ core reversibly encapsulated several organic guest molecules through electrostatic interactions in its crystals. Hence, the corresponding dinuclear complex, [Cu₂(L²)₂] ( 2 , H₂L²=1,5-dihydroxy-1,5-bis(pentafluorophenyl)-1,4-pentadien-3-one), was prepared to enhance guest recognition and the ability to separate molecular mixtures. Complex 2 comprises a Cu₂O₆ core and four pentafluorophenyl groups. In crystal 2 , cavities are formed on the axial sites of the metal core that are surrounded by pentafluorophenyl groups. The crystal of 2 encapsulates various guest molecules, that is, benzene ( 3 ), toluene ( 4 ), xylene ( 5 ), mesitylene ( 6 ), durene ( 7 ), and anisole ( 8 ). X-ray crystallographic and thermogravimetric (TG) studies show that three guest molecules are present in the crystal cavities. The number of guest molecules found in complex 2 was higher than that in complex 1 , for example, ( 2 )₃ ⋅ ( 6 )₁₀> 1⋅ ( 6 )₂, ( 2 )₂ ⋅ ( 7 )₇> 1⋅7 , or 2⋅ ( 8 )₃> 1⋅ ( 8 )₂. Naphthalene ( 9 ), was encapsulated in 2 to give 2⋅ ( 9 )₃, but not in 1 . In the crystal of complex 2 , heteromolecular guest encapsulation was confirmed, designated as 2⋅ ( 3 )₂ ⋅9 . TG analysis indicates that the thermal stability of the guest-included crystals of 2 is higher than that of 1 .     

Potential Applications of Cucurbit[n]urils and Their Derivatives in the Capture of Hazardous Chemicals

Cucurbit[n]urils (Q[n]s) are a relatively young family of macrocycles, consisting of glycoluril units bridged by methylene groups, and their unique structures have attracted extensive attention from chemists in recent decades. Due to the presence of a rigid hydrophobic inner cavity and two polar outer portals lined with carbonyl groups, Q[n]s not only encapsulate guest species into the cavity, but also coordinate with metal ions/clusters. Considerable achievements have been obtained in the fields of Q[n]s-based host–guest chemistry, coordination chemistry, as well as the combination of host–guest and coordination chemistry. Furthermore, the outer surface of Q[n]s has been demonstrated to be capable of interacting with definite species to generate supramolecular architectures in recent years. With more in-depth research into Q[n]s, their application studies have also emerged as a hot topic. This Minireview focuses on recent advances in the potential applications of solid-state materials based on Q[n]s and their derivatives for the capture and adsorption of hazardous chemicals from a solution or a gas mixture.     

A Flexible Copper(I)‐Complexed [4]Rotaxane Containing Two Face‐to‐Face Porphyrinic Plates that Behaves as a Distensible Receptor

A new cyclic [4]rotaxane composed of two flexible bis‐macrocycles and two rigid axles is described. Each bis‐macrocycle consists of two rings attached to antipodal meso positions of a central Zn porphyrin through single C? C bonds. Each ring incorporates a 2,9‐diphenyl‐1,10‐phenanthroline chelation site. The axles contain two coplanar bidentate sites derived from the 2,2′‐bipyridine motif. The building blocks were assembled by using a one‐pot threading‐and‐stoppering reaction, which afforded the [4]rotaxane in 50 % yield. The “gathering‐and‐threading” effect of copper(I) was utilised in the formation of a [4]pseudorotaxane, which was immediately converted to the corresponding [4]rotaxane by a quadruple CuAAC stoppering reaction. The rotaxane contains two face‐to‐face zinc porphyrins, which allowed the coordination of ditopic guest substrates. The rotaxane host showed remarkable flexibility and was able to adjust its conformation to the guest size. It can be distended and accommodate rod‐like guests of 2.6 to 15.8 Å in length.     

One-Step Synthesis of Cyclophanes as Crystalline Sponge and Their [2]Catenanes through SNAr Reactions

This work reports that cyclophanes and their [2]catenanes were synthesized by the S_NAr reactions of disubstituted adamantanes bearing halophenol units and 3,6-dichlorotetrazine in moderate yields. In the crystalline state, the cyclophanes had hexagonal structures with a cavity. The [2]catenanes were composed of two macrocycles that were singly interlocked and orthogonally arranged, indicating the construction from eight component molecules through eight C−O bonds in a one-step reaction in up to 33 % yield. The cyclophanes were assembled to afford a supramolecular organic framework in the solid state, which exhibited permanent intrinsic porosity and adsorption of leaf alcohol or aldehyde in a single-crystal to single-crystal fashion. The molecular structures of the liquid guests were determined by single-crystal X-ray analysis. The formation of catenanes and the use of cyclophane-based porous crystals in the crystalline sponge method may be largely ascribed to the solvophobic effects and the van der Waals interactions that originate in the aliphatic and bulky nature of the adamantane units.     

A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and Dimeric Adapter Protein 14-3-3

Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14-3-3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation-dependent mono- or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)-based supramolecular system, which in conjunction with the 14-3-3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine–glycine–glycine (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8-induced dimerization of the ERα epitope augmented its affinity towards 14-3-3 through a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex revealed molecular insight into the multiple supramolecular interactions between the protein, the peptide, and Q8.     

Shaping a Porphyrinoid Frame by Heteroatoms Extrusion: Formation of an Expanded [22]Triphyrin(6.6.0)

An aromatic expanded triphyrin, [22]triphyrin(6.6.0) 2 , containing a pyrrole unit, a bipyrrole moiety, and annulene links, was obtained from a tellurium-containing precursor meso-tetraaryl-26,28-ditellurasapphyrin 1 . The reaction path proceeds through an acid-promoted tellurium extrusion from 1 yielding directly 2 , characterized in a dicationic form by X-ray crystallography. In solution the neutral macrocycle 2 reveals flexibility typical for annulenes and it exists as a mixture of conformers that differ by the configuration of the annulene fragments, as proven by ¹H NMR studies and analyzed by DFT methods. The conformation is controlled by protonation state, the nature of an interacting anion, solvent identity, and by interaction with water.     

Sulfate‐Selective Binding and Sensing of a Fluorescent [3]Rotaxane Host System

The chloride‐templated synthesis of a novel [3]rotaxane, capable of binding anionic guests, and incorporating a naphthalene group for fluorescence sensing is reported. Extensive ¹H NMR titration studies were used to probe the anion binding selectivity of the system. The rotaxane selectively recognises sulfate, undergoing an induced conformational change upon sulfate binding to form a 1:1 stoichiometric sandwich‐type complex, concomitant with significant quenching of the fluorescence. Binding of mono‐anionic guests results in the formation of a 2:1 stoichiometric guest–host complex, and a modest enhancement of the emission. Addition of an excess of sulfate in non‐competitive solvent also results in a 2:1 emissive complex.     

Synthesis and Binding Properties of a Tren-Capped Hexahomotrioxacalix[3]arene

The straightforward synthesis of a new hexahomotrioxacalix[3]arene-based ligand capped by a tren subunit was developed and the binding properties of the corresponding zinc complex were explored by NMR spectroscopy. Similarly to the closely related calix[6]tren-based systems, the homooxacalixarene core ensures the mononuclearity of the zinc complex and the metal center displays a labile coordination site for exogenous guests. However, very different host–guest properties were observed: i) in CDCl₃, the zinc complex strongly binds a water molecule and is reluctant to recognize other neutral guests, ii) in CD₃CN, the exo-coordination of anions prevails. Thus, in strong contrast to the calix[6]tren-based systems, the coordination of neutral guests that thread through the small rim and fill the polyaromatic cavity was not observed. This unique behaviour is likely due to the fact that the 18-membered ethereal macrocycle is too small to let a molecule threading through it. This work illustrates the key role played by the second coordination sphere in the binding properties of metal complexes.     

A Dual‐Response [2]Rotaxane Based on a 1,2,3‐Triazole Ring as a Novel Recognition Station

Two novel multilevel switchable [2]rotaxanes containing an ammonium and a triazole station have been constructed by a Cu^I‐catalyzed azide–alkyne cycloaddition reaction. The macrocycle of [2]rotaxane containing a C6‐chain bridge between the two hydrogen bonding stations exhibits high selectivity for the ammonium cation in the protonated form. Interestingly, the macrocycle is able to interact with the two recognition stations when the bridge between them is shortened. Upon deprotonation of both [2]rotaxanes, the macrocycle moves towards the triazole recognition site due to the hydrogen‐bond interaction between the triazole nitrogen atoms and the amide groups in the macrocycle. Upon addition of chloride anion, the conformation of [2]rotaxane is changed because of the cooperative recognition of the chloride anion by a favorable hydrogen‐bond donor from both the macrocycle isophthalamide and thread triazole CH proton.