Macrocyclic Components Research Articles

Active-Metal Template Synthesis of a Halogen-Bonding Rotaxane for Anion Recognition.

The synthesis of an all‐halogen‐bonding rotaxane for anion recognition is achieved by using active‐metal templation. A flexible bis‐iodotriazole‐containing macrocycle is exploited for the metal‐directed rotaxane synthesis. Endotopic binding of a CuI template facilitates an active‐metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper‐template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen‐bond donors into the rotaxane’s interlocked binding cavity to facilitate anion recognition.

Shielded alkyl-functionalised rotaxane host cavities for improved anion recognition

The synthesis and anion recognition properties of four novel [2]rotaxane host architectures containing additional alkyl functionality integrated within macrocyclic and axle components to shield the binding cavity from the solvent are described. The rotaxane species containing a tetra(methyl)-functionalised macrocycle component is found to be a weaker anion complexant than the equivalent unfunctionalised receptor, which is likely due to steric hindrance restricting the anion's access to the interlocked cavity. Rotaxane molecules containing tetra(methyl)-functionalised axle components are also investigated, and the additional alkyl functionality serves to enhance anion binding affinity and selectivity when incorporated within the axle's flexible ethylene linkages. Moreover, the equivalent unfunctionalised rotaxane displays a rare preference for oxoanions over chloride guest species.

Construction of a hetero pseudo[2]rota[2]catenane

Abstract A novel ammonium template containing three ammonium sites was synthesized. Two ammoniums located on the linear component served as template for cucurbit[6]uril to form the CB-based pseudo [2]rotacane while another one located on the macrocyclic component played a role of template for clipping reaction. As a result of a “threading-followed-by-clipping” approach, a novel hetero pseudo [2]rota[2]catenane was successfully constructed.

(68) Ga]-HP-DO3A-nitroimidazole: a promising agent for PET detection of tumor hypoxia.

The goal of this study is to evaluate a new (68) Ga-based imaging agent for detecting tumor hypoxia using positron emission tomography (PET). The new hypoxia targeting agent reported here, [(68) Ga]-HP-DO3A-nitroimidazole ([(68) Ga]-HP-DO3A-NI), was constructed by linking a nitroimidazole moiety with the macrocyclic ligand component of ProHance®, HP-DO3A. The hypoxia targeting capability of this agent was evaluated in A549 lung cancer cells in vitro and in SCID mice bearing subcutaneous A549 tumor xenografts. The cellular uptake assays showed that significantly more [(68) Ga]-HP-DO3A-NI accumulates in hypoxic tumor cells at 30, 60 and 120 min than in the same cells exposed to 21% O2 . The agent also accumulated in hypoxic tumors in vivo to give a tumor/muscle ratio (T/M) of 5.0 ± 1.2 (n = 3) as measured by PET at 2 h post-injection (p.i.). This was further confirmed by ex vivo biodistribution data. In addition, [(68) Ga]-HP-DO3A-NI displayed very favorable pharmacokinetic properties, as it was cleared largely through the kidneys with little to no accumulation in liver, heart or lung (%ID/g < 0.5%) at 2 h p.i. The specificity of the agent for hypoxic tissues was further validated in a comparative study with a control compound, [(68) Ga]-HP-DO3A, which lacks the nitroimidazole moiety, and by PET imaging of tumor-bearing mice breathing air versus 100% O2 . Given the commercial availability of cGMP (68) Ge/(68) Ga generators and the ease of (68) Ga labeling, the new agent could potentially be widely applied for imaging tumor hypoxia prior to radiation therapy.

Molecular dynamics simulation of a cucurbituril based molecular switch triggered by pH changes

Molecular Dynamics (MD) simulations are performed for a cucurbituril-pseudorotaxane system that functions as a molecular switch in which the movement of the macrocycle (CB) component of the rotaxane between two sites is triggered by an appropriate change in pH. The system consists of a CB bead and a fluorenyltriamine string in aqueous solution. Examining the extracted snapshots reveals that the fluorenyl ring bends toward the CB rim when it locates at the butyl moiety, and it becomes aligned with the rest of the guest when it locates at the hexyl moiety. No movement of the macrocycle between the possible positions for CB6 complexes for the fully protonated or the diprotonated guests was observed during the 20ns simulation. However, such movement was observed in the case of CB7 and CB8. Umbrella sampling was used to obtain the potential of mean force curves, which demonstrates the existence of an energy barrier between the two sites. The height of the barrier was found to decrease as the size of the CB increases. Molecular Mechanics Poisson–Boltzmann Surface Area results indicate that the host–guest electrostatic interactions have the largest contribution to the stability of the complexes.

On the Iron(V) Reactivity of an Aggressive Tail‐Fluorinated Tetraamido Macrocyclic Ligand (TAML) Activator

AbstractThe electronic properties of iron tetraamido macrocyclic ligand (TAML) activators of peroxides can be finely and coarsely tuned by varying the substituents on the “head” and “tail” macrocyclic components, respectively. By examining the reactivity of the TAML oxidoiron(V) complex with head‐NO2 and tail‐F substituents, one is able to compare the impact of significantly reduced macrocyclic tetraamide donor capacity on fundamental processes such as hydrogen‐atom abstraction, oxygen‐atom transfer, and electron transfer by using prior studies with more electron‐rich TAML systems. Herein, we demonstrate that the oxidoiron(V) form 3c can be generated by treatment of [Fe{4‐NO2C6H3‐1,2‐(N2COCMe2N3CO)2CF2(Fe–N2)(Fe–N3)}(OH2)]– (1c) with m‐chloroperoxybenzoic acid (mCPBA) in MeCN at –40 °C. The oxidation proceeds through the intermediacy of the μ‐oxo[iron(IV)]2 dimer. The overall rate of the FeIII→FeV conversion by mCPBA is slightly faster for 1c than that of its less electron‐rich precursor [Fe{C6H4‐1,2‐(N1COCMe2N2CO)2CMe2(Fe–N1)(Fe–N2)}(OH2)]– (1a). Nevertheless, the oxidative reactivity of 3c toward thioanisole and the hydrocarbons ethylbenzene and cyclohexane exceeds that of 3a by 4.3, 2.1, and 2.6 times, respectively. The reactivity of 3c is significantly greater towards ethylbenzene than that of the oxidoiron(V) species 3b derived from [Fe{C6H4‐1,2‐(N1COCMe2N2CO)2NMe(Fe–N1)(Fe–N2)}(OH2)]– (1b).

A redox-controllable molecular switch based on weak recognition of BPX26C6 at a diphenylurea station.

The Na+ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station.

Aggregation-induced emission behavior of a pH-controlled molecular shuttle based on a tetraphenylethene moiety.

Tetraphenylethene (TPE) with aggregation-induced emission (AIE) behavior as a popular backbone is applied widely in the construction of functional supramolecular systems. In this work, a TPE-based linear molecule having amide and amine units is synthesized. Its ammonium template is used to construct the N-hetero crown ether-based [2]rotaxane by the template-directed clipping approach. Their structures are well-characterized by NMR, MALDI-TOF-MS and elemental analysis. Owing to the existence of the amide unit, [2]rotaxane possesses the function of a molecular shuttle. The shuttling motion of the macrocycle component between the ammonium station and the amide station can be driven by external acid-base stimuli in solution, accompanied by changes in visual behavior. Investigation on their AIE behavior shows that (1) ammonium reaches the aggregation state almost in the presence of same water with the deprotonated form of ammonium; (2) the [2]rotaxane that the macrocycle component locates at the site of ammonium forms the aggregation state in the presence of less water than the deprotonated [2]rotaxane that the macrocycle component locates at the site of the amide, attributed to stronger interaction between the crown ether component and the TPE unit of the template component when the distance between the two is shorter. The result indicates that the shuttling motion of the macrocycle component can adjust the aggregation state of AIE molecules.

A fluorescent bistable [2]rotaxane molecular switch on SiO₂ nanoparticles.

A fluorescent bistable [2]rotaxane terminated with an alkyne functional group was constructed and immobilized onto the surface of SiO2 nanoparticles through click reaction. The shuttling motion of the macrocycle component between two different stations was driven by external acid-base stimuli both in solution and on SiO2 nanoparticles, accompanied by visual fluorescence changes.

Synthesis and characterization of new azobenzene-containing bis pentacyanoferrate(II) stoppered push–pull [2]rotaxanes, with α- and β-cyclodextrin. Towards highly medium responsive dyes

The solvatochromic behavior of novel synthesized azo-containing viologen-based rotaxanes, combining push–pull linear and α or β-cyclodextrin macrocyclic components is examined. These rotaxanes are stoppered by pentacyanoferrate(II) units. The latter stabilize these systems and furthermore act as strong electron donors. These units are linked to strong electron withdrawing viologen units thus giving rise to an exceptionally intense solvatochromic behavior. Suitable solvent polarity scales and Linear Solvation Energy Relationships (LSERs) were employed in order to rationalize the solvent polarity effects observed, both specific and non-specific ones. The results for the title compounds as well as their Cyclodextrin-Free-Dumbbell (CFD) like analogue, are compared to recent published solvatochromic data regarding similar smaller pentacyanoferrate(II) complexes as well as other highly solvatochromic compounds. Structural effects on the solvatochromic intensity as well as the contribution of different solvent-solute interactions are rationalized and quantified.

Iodide-induced shuttling of a halogen- and hydrogen-bonding two-station rotaxane.

The first example of utilizing halogen-bonding anion recognition to facilitate molecular motion in an interlocked structure is described. A halogen-bonding and hydrogen-bonding bistable rotaxane is prepared and demonstrated to undergo shuttling of the macrocycle component from the hydrogen-bonding station to the halogen-bonding station upon iodide recognition. In contrast, chloride-anion binding reinforces the macrocycle to reside at the hydrogen-bonding station.

Iodide‐Induced Shuttling of a Halogen‐ and Hydrogen‐Bonding Two‐Station Rotaxane

AbstractThe first example of utilizing halogen‐bonding anion recognition to facilitate molecular motion in an interlocked structure is described. A halogen‐bonding and hydrogen‐bonding bistable rotaxane is prepared and demonstrated to undergo shuttling of the macrocycle component from the hydrogen‐bonding station to the halogen‐bonding station upon iodide recognition. In contrast, chloride‐anion binding reinforces the macrocycle to reside at the hydrogen‐bonding station.

Inside Back Cover: An All-Halogen Bonding Rotaxane for Selective Sensing of Halides in Aqueous Media (Angew. Chem. Int. Ed. 43/2014)

Combining halogen bonding …︁ with an optical probe in an interlocked host design leads to a potent anion sensory system. As P. D. Beer et al. show in their Communication on page 11458 ff, an all-halogen-bonding rotaxane host with a photoactive rhenium(I) bipyridyl center in the macrocyclic component can optically sense halide anions by luminescence, with a high binding affinity and selectivity for iodide ions. Image: Dr. Karl Harrison.

An All‐Halogen Bonding Rotaxane for Selective Sensing of Halides in Aqueous Media

AbstractThe synthesis and anion binding properties of the first rotaxane host system to bind and sense anions purely through halogen bonding, is described. Through a combination of polarized iodotriazole and iodotriazolium halogen bond donors, a three‐dimensional cavity is created for anion binding. This rotaxane incorporates a luminescent rhenium(I) bipyridyl metal sensor motif within the macrocycle component, thus enabling optical study of the anion binding properties. The rotaxane topology was confirmed by single‐crystal X‐ray structural analysis, demonstrating halogen bonding between the electrophilic iodine atoms and chloride anions. In 50 % H2O/CH3CN solvent mixtures the rotaxane host exhibits strong binding affinity and selectivity for chloride, bromide, and iodide over a range of oxoanions.

An all-halogen bonding rotaxane for selective sensing of halides in aqueous media.

The synthesis and anion binding properties of the first rotaxane host system to bind and sense anions purely through halogen bonding, is described. Through a combination of polarized iodotriazole and iodotriazolium halogen bond donors, a three-dimensional cavity is created for anion binding. This rotaxane incorporates a luminescent rhenium(I) bipyridyl metal sensor motif within the macrocycle component, thus enabling optical study of the anion binding properties. The rotaxane topology was confirmed by single-crystal X-ray structural analysis, demonstrating halogen bonding between the electrophilic iodine atoms and chloride anions. In 50% H2O/CH3CN solvent mixtures the rotaxane host exhibits strong binding affinity and selectivity for chloride, bromide, and iodide over a range of oxoanions.

Structural Study of Triazole and Amide Containing Anion-Templated Pseudorotaxanes

The ability of a range of halides and oxoanions to template pseudorotaxane formation between an isophthalamide containing macrocycle and either bis-triazole pyridinium or bis-amide pyridinium threading components was investigated. Solution 1H NMR experiments reveal that all of the studied anions (Cl–, Br–, I–, NO3–, HSO4–, OAc–, and BzO–) can template interpenetrated assemblies. The solid-state structures of nine of the pseudorotaxanes were determined by single crystal X-ray structural analysis. In the solid state, the oxoanions nitrate, acetate and benzoate display much stronger hydrogen bonding with the macrocycle and threading components than the halide anions. Conversely, aromatic donor–acceptor contacts between the macrocycle and thread are significantly longer in the oxoanion templated pseudorotaxanes, presumably due to the greater steric demands of these larger templates.

Construction of rotacatenanes using rotaxane and catenane frameworks.

The construction of novel mechanically interlocked structures has become a topic of great current interest due to the requirements of topology and their potential application in molecular machines and devices. Rotaxane and catenane as two basic topological frameworks can be used to construct the fused structures. In the current investigation, a class of novel ammonium backbones were synthesized. The ammonium group incorporated in the linear part of the molecule can be used for templating rotaxane formation while the macrocyclic part of the molecule can be used for templating catenane formation. Accordingly, they were subjected to dynamic covalent chemistry, resulting in a series of [n]rota[n]catenane structures (n = 2, 3, 4). In this process, the N-hetero crown ethers were installed on ammonium template sites of linear and macrocyclic components all at once by a template-directed clipping reaction. The results showed that these novel building blocks could be assembled with high efficiencies. Finally, this investigation provides a foundation for future studies aimed at constructing complicated integrated structures or polymers with multiple topological units.

Increased Halide Recognition Strength by Enhanced Intercomponent Preorganisation in Triazolium Containing [2]Rotaxanes

Three triazolium-based [2]rotaxanes containing different sized axle and macrocycle components were synthesised in good yields (40-57%) through chloride anion templation. The anion recognition properties of the interlocked receptor systems were investigated using (1)H NMR titration experiments: all three rotaxanes display impressive selectivities for halide anions over the more basic oxoanion acetate. The rotaxanes incorporating shorter, more rigid axle components with aryl-substituted triazolium groups display substantially higher anion binding affinities than those with longer, bis-alkyl-substituted heterocycles, which is attributed to the increased intercomponent preorganisation afforded by the smaller axle component. Computational DFT and molecular dynamics simulations composed of unconstrained and umbrella sampling simulations corroborate the experimental observations.

Anion Sensing by Solution‐ and Surface‐Assembled Osmium(II) Bipyridyl Rotaxanes

We report the preparation of [2]rotaxanes containing an electrochemically and optically active osmium(II) bipyridyl macrocyclic component mechanically bonded with cationic pyridinium axles. Such interlocked host systems are demonstrated to recognise and sense anionic guest species as shown by 1H NMR, luminescence and electrochemical studies. The rotaxanes can be surface assembled on to gold electrodes through anion templation under click copper(I)-catalysed Huisgen cycloaddition conditions to form rotaxane molecular films, which, after template removal, respond electrochemically and selectively to chloride.

Use of Cleavable Coordinating Rings as Protective Groups in the Synthesis of a Rotaxane with an Axis that Incorporates More Chelating Groups Than Threaded Macrocycles

A new methodology allowing preparation of a linear "unsaturated" [3]rotaxane consisting of an axis incorporating more coordination sites than threaded rings was developed. It was based on the preliminary synthesis of a "saturated" [5]rotaxane consisting of a four-chelating site axis threaded through four macrocyclic components, two of them being cleavable rings incorporating a lactone function and the two others being "secure" non-cleavable rings. The stoppering reaction was based on click chemistry. Subsequently, cleavage and removal of the two lactone-containing macrocycles from the [5]rotaxane in basic medium afforded the desired "unsaturated" [3]rotaxane in quantitative yield.