Reactions in Endohedral Functionalized Cages

The introduction of enhanced functionalization is a key aspect in the current design of cage chemistry. At the moment, several approaches are intensively investigated. The synthesis of cage compounds that display endohedral functionalization plays a key role among them. Here, the studies of reactions that occur in endohedral-functionalized cage compounds is reviewed. After an introduction in current trends in cage-chemistry the discussion of reactions in endohedral-cage compounds is divided into three sections. These are: 1) Endohedral groups that are by themselves functional, 2) endohedral groups that can bind to a transition-metal complex and 3) endohedral groups that can bind by themselves to a metal. The article closes with an outlook on additional current developments in the field of endohedral-functionalized cage-compounds, which may contribute in the future towards reactivity in cage compounds.     

超分子化学发展简介

本文综述了超分子化学的定义 , 范围及内容. 着重介绍了分子识别, 分子自组装, 超分子催化, 超分子器件及超分子材料等概念. 对由此可能形成的新的前沿科学如分子电子学, 分子离子学, 分子光子学及超分子工艺学等作了扼要介绍 .     

Self-Assembled Multivalent Ag-SR Coordination Polymers with Phosphatase-Like Activity

We show herein the phosphatase-like catalytic activity of coordination polymers obtained after adding Ag⁺-ions to thiols bearing hydrophobic alkyl chains terminated with a 1,4,7-triazacyclononane (TACN) group. The subsequent addition of Zn²⁺ -ions to the self-assembled polymers resulted in the formation of multivalent metal coordination polymers capable of catalysing the transphosphorylation of an RNA-model compound (2-hydroxypropyl-4-nitrophenyl phosphate, HPNPP) with high reactivity. Analysis of a series of metal ions showed that the highest catalytic activity was obtained when Ag⁺-ions were used as the first metal ions to construct the backbone of the coordination polymer through interaction with the -SH group followed by Zn²⁺-ions as the second metal ions complexed by the TACN-macrocycle. Furthermore, it was demonstrated that the catalytic activity could be modulated by changing the length of the hydrophobic alkyl chain.     

Emergent Molecular Recognition through Self‐Assembly: Unexpected Selectivity for Hyaluronic Acid among Glycosaminoglycans

Oligophenylenevinylene (OPV)‐based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4‐sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self‐assembly: H‐type aggregate for HEP with 16‐times FL increase and J‐type aggregate for HA with 93‐times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self‐assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer‐related diseases.     

Triazolyl‐Based Molecular Gels as Ligands for Autocatalytic ‘Click’ Reactions

The catalytic performance of triazolyl‐based molecular gels was investigated in the Huisgen 1,3‐dipolar cycloaddition of alkynes and azides. Low‐molecular‐weight gelators derived from l ‐valine were synthesized and functionalized with a triazole fragment. The resultant compounds formed gels either with or without copper, in a variety of solvents of different polarity. The gelators coordinated Cu^I and exhibited a high catalytic activity in the gel phase for the model reaction between phenylacetylene and benzylazide. Additionally, the gels were able to participate in autocatalytic synthesis and the influence of small structural changes on their performance was observed.     

Self-Assembly of a Trithioorthoformate-Capped Cyclophane and Its Endohedral Inclusion of a Methine Group

An unusual trithioorthoformate-capped cyclophane cage was assembled via antimony-activated iodine oxidation of thiols as confirmed by ¹H-NMR spectroscopy and X-ray crystallography. The disulfide bridges can undergo desulfurization with hexamethylphosphorous triamide (HMPT) at ambient temperature to capture a trithioether cyclophane cage capped by the trithioorthoformate. In both cages a methine proton points directly into the small cavity. This unexpected structure is hypothesized to have formed as a result of haloform insertion during oxidation.     

A Chiral Recognition System Orchestrated by Self‐Assembly: Molecular Chirality,Self‐Assembly Morphology,and Fluorescence Response

The newly developed oligophenylenevinylene (OPV)‐based fluorescent (FL) chiral chemosensor (OPV‐Me) for the representative enantiomeric guest, 1,2‐cyclohexanedicarboxylic acid (1,2‐CHDA: RR ‐ and SS ‐form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV‐Me self‐assembly: RR ‐CHDA directed the fibrous supramolecular aggregate, whereas SS ‐CHDA directed the finite aggregate. The consequent FL intensity toward RR ‐CHDA was up to 30 times larger than that toward SS ‐CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV‐Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self‐assembly.     

Post-Synthesis Conversion of an Unstable Imine Cage to a Stable Cage with Amide Moieties Towards Selective Receptor for Fluoride

Synthesis of robust covalent macrocycles/cages via multiple amide-bond forming reaction is highly challenging and generally it needs multistep reactions. One-pot reaction of appropriate di-/tri-acyl chloride with a diamine generally results polymers or oligomers instead of discrete architectures. To overcome this limitation, a strategy is reported here using dynamic imine chemistry for facile construction of imine-based macrocycle and cage upon treatment of a diamine with di- and tri-aldehydes respectively, followed by post-synthesis one-step conversion of imine bonds to amides to form the desired robust macrocycle and cage containing multiple amide bonds. While the macrocycle was found to form aggregates in DMSO, the cage was intact without any aggregation. Six amide groups in the confined pocket of the cage made it an ideal receptor for selective binding of fluoride with very high selectivity (∼3 10³ fold) over chloride, and it was silent towards other halides, phosphate, and other oxyanions.     

Molecular Recognition by Zn(II)-Capped Dynamic Foldamers

Two α-aminoisobutyric acid (Aib) foldamers bearing Zn(II)-chelating N-termini have been synthesized and compared with a reported Aib foldamer that has a bis(quinolinyl)/mono(pyridyl) cap (BQPA group). Replacement of the quinolinyl arms of the BQPA-capped foldamer with pyridyl gave a BPPA-capped foldamer, then further replacement of the linking pyridyl with a 1,2,3-triazole gave a BPTA-capped foldamer. Their ability to relay chiral information from carboxylate bound to Zn(II) at the N-terminus to a glycinamide-based NMR reporter of conformational preference at the C-terminus was measured. The importance of the quinolinyl arms became readily apparent, as the foldamers with pyridyl arms were unable to report on the presence of chiral carboxylate in acetonitrile. Low solubility, X-ray crystallography and ¹H NMR spectroscopy suggested that interfoldamer interactions inhibited carboxylate binding. However changing solvent to methanol revealed that the end-to-end relay of chiral information could be observed for the Zn(II) complex of the BPTA-capped foldamer at low temperature.     

Tunable Fullerene Affinity of Cages,Bowls and Rings Assembled by PdII Coordination Sphere Engineering

For metal-mediated host compounds, the development of strategies to reduce symmetry and introduce multiple functionalities in a non-statistical way is a challenging task. We show that the introduction of steric stress around the coordination environment of square-planar Pd^II cations and bis-monodentate nitrogen donor ligands allows to control the size and shape of the assembled product, from [Pd₂L₄] cages over [Pd₂L₃] bowl-shaped structures to [Pd₂L₂] rings. Therefore, banana-shaped ligand backbones were equipped with pyridines, two different quinoline isomers and acridine, the latter three introducing steric congestion through hydrogen substituents on annelated benzene rings. Differing behavior of the four resulting hosts towards the binding of C₆₀ and C₇₀ fullerenes was studied and related to structural differences by NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction. The three cages based on pyridine, 6-quinoline or 3-quinoline donors were found to either bind C₆₀, C₇₀ or no fullerene at all.     

Multimetallic Architectures from the Self‐assembly of Amino Acids and Tris(2‐pyridylmethyl)amine Zinc(II) Complexes: Circular Dichroism Enhancement by Chromophores Organization

Stereodynamic optical probes are becoming very popular for their capability to act as molecular sensors for the determination of the enantiomeric excess (ee) of chiral compounds. Herein, we describe a new molecular architecture formed by the self‐assembly of three zinc metal ions, two modified tris(2‐pyridylmethyl)amine ligands, and two amino acids. This system is the structural and functional serendipitous evolution of our previous probe for the determination of amino acids ee. In the new system, one of the metals templates in close proximity two chromophores enhancing their exciton coupling.     

Programmable Self‐Assembly of Heterometallic Palladium(II)–Copper(II) 1D Grid‐Chain using Dinuclear Palladium(II) Corners with Pyrazole–Carboxylic Acid Ligands

A novel heterometallic diPd^II–diCu^II grid‐chain, {[(bpy)₄Pd₄Cu₂L₄](NO₃)₄}_n ( 2 ; bpy=2,2′‐bipyridine), was synthesized through a programmable self‐assembly approach from the molecular corners [(bpy)₂Pd₂(HL)(L)](NO₃) ( 1 ) as linkers with Cu^II nitrate by using the bifunctional H₂L ligand featuring primary (pyrazole) and secondary (benzoic acid) groups. Structural analysis revealed that 1D structure 2 consists of one [Cu₂(O₂CPh)₄]_n unit as a bridge and two [(bpy)₂Pd₂L₂]_n corners. Additionally, the catalytic effect of the heterometallic synergy on the Suzuki coupling reaction by using 2 was further explored.     

A Cyclopeptide‐Derived Molecular Cage for Sulfate Ions That Closes with a Click

The 2:1 sandwich‐type complexes formed between a cyclopeptide with alternating L ‐proline and 6‐aminopicolinic acid subunits and inorganic anions can be stabilized by covalently linking a tris‐alkyne and a tris‐azide derivative of this peptide through copper‐catalyzed azide–alkyne cycloaddition. The resulting triply linked bis‐cyclopeptide can interact with anions such as sulfate ions in aqueous solution by including them into the cavity between the two cyclopeptide rings, where they can form hydrogen bonds to amide NH groups, distributed along the inner surface. The binding kinetics of this system differ significantly from those of a bis‐cyclopeptide that contains only one linker because the rate of guest exchange is considerably slower. Thermodynamically, the stability of the sulfate complex of the triply linked bis‐cyclopeptide approaches a log K_a value of 6 in H₂O/CH₃OH 1:1 (v/v) which is, however, only approximately one order of magnitude larger than affinity of the more flexible monolinked analogue. Titration calorimetry revealed that this behavior is mainly due to the change in the binding enthalpy from exothermic to endothermic upon increasing the number of linkers. Results from NMR spectroscopy and X‐ray crystallography indicate that the mono‐ and triply linked bis‐cyclopeptides adopt similar conformations in their complexes with sulfate ions, but the complex formation is enthalpically unfavorable for the cage. The substantial entropic contribution to sulfate complexation of this receptor more than compensates for this disadvantage, so that the overall sulfate affinity of both bis‐cyclopeptides ends up in the same range. These investigations provide important insight into the structure–property relationships of such receptors, thus leading the way to further structural improvement.     

A Multifunctional,Charge-Neutral,Chiral Octahedral M12L12 Cage

A chiral, octahedral M₁₂L₁₂ cage, which is charge neutral and contains an internal void of about 2000 ų, is reported. The cage was synthesised as an enantiopure complex by virtue of amino-acid-based dicarboxylate ligands, which assemble around copper paddlewheels at the vertices of the octahedron. The cage persists in solution with retention of the fluorescence properties of the parent acid. The solid-state structure contains large pores both within and between the cages, and displays permanent porosity for the sorption of gases with retention of crystallinity. Initial tests show some enantioselectivity of the cage towards guests in solution.     

萘酰氨修饰β-环糊精及其铜配合物对萘衍生物的分子识别

用荧光光谱滴定技术分别测定了β-环糊精(1)、单-[6-(1-萘酰氨基)-乙基氨基-6-脱氧]-β-环糊精(2)、单-[6-(1-萘酰氨基)-二乙基二氨基-6-脱氧]-β-环糊精(3)及其相应的铜配合物(4、5)在25 ℃时，pH为7.20的缓冲溶液中与几种萘衍生物形成的超分子配合物的稳定常数。结果表明，化合物2、3与大部分β-萘衍生物形成超分子配合物的稳定性大于α-萘衍生物。铜键合修饰的环糊精4、5扩展了母体环糊精的键合能力，其中主体5与2-萘酚(2-NO)形成的稳定常数是母体环糊精的35倍,且引入铜(II)后，修饰环糊精的分子选择性提高。从主-客体的尺寸/形状匹配和多重识别等方面探讨了分子识别的机理。     

Reactivity and Selectivity of Iminium Organocatalysis Improved by a Protein Host

There has been growing interest in performing organocatalysis within a supramolecular system as a means of controlling reaction reactivity and stereoselectivity. Here, a protein is used as a host for iminium catalysis. A pyrrolidine moiety is covalently linked to biotin and introduced to the protein host streptavidin for organocatalytic activity. Whereas in traditional systems stereoselectivity is largely controlled by the substituents added to the organocatalyst, enantiomeric enrichment by the reported supramolecular system is completely controlled by the host. Also, the yield of the model reaction increases over 10‐fold when streptavidin is included. A 1.1 Å crystal structure of the protein–catalyst complex and molecular simulations of a key intermediate reveal the chiral scaffold surrounding the organocatalytic reaction site. This work illustrates that proteins can be an excellent supramolecular host for driving stereoselective secondary amine organocatalysis.     

Photoresponsive Cyclodextrin‐Covered Nanocontainers and Their Sol‐Gel Transition Induced by Molecular Recognition

Springing the trap : Cyclodextrin‐covered mesoporous silica nanoparticles with photocleavable linkers exhibit photoinduced release characteristics and a sol–gel transition that is induced by molecular recognition (see picture). Upon exposure to UV light, the guest molecules were released from the pore by removal of the CD “gatekeeper”, which was linked on the surface of the silica nanoparticle through a photocleavable o‐nitrobenzyl ester moiety.

     

What anions do inside a receptor's cavity: a trifurcate anion receptor providing both electrostatic and hydrogen-bonding interactions

The trifurcate receptor 1(3+) forms stable 1:1 complexes with halide and oxo anions in MeCN solution, as shown by spectrophotometric and 1H NMR experiments, and selectively recognizes chloride (lg K(ass) > 7) in the presence of fluoride and bromide. The high stability reflects the receptor's ability to donate up to six hydrogen bonds (from three pyrrole N-H and three C-H fragments, polarized by the proximate positive charge) to the included anion. Addition of an excess of more basic anions (F- and CH3COO-) induces stepwise deprotonation of the N-H groups, an event signalled by the appearance of a bright yellow color. Crystal and molecular structures are reported for the complex with NO3(-) and a capsule consisting of two interconnected trifurcate subunits, one of which includes an H-bound Br- ion, while the other is doubly deprotonated and includes an H-bound water molecule. Finally, evidence is given for the formation in solution of an authentic complex of OH-, in which H-bound hydroxide is included within the cavity of 1(3+).     

Molecular Recognition of Zwitterions with Artificial Receptors

Many biomolecules exist as internal ion pairs or zwitterions within a biologically relevant pH range. Despite their importance, the molecular recognition of this type of systems is specially challenging due to their strong solvation in aqueous media, and their trend to form folded or self‐assembled structures by pairing of charges of different sign. In this Minireview, we will discuss the molecular recognition of zwitterions using non‐natural, synthetic receptors. This contribution does not intend to make a full in‐depth revision of the existing research in the field, but a personal overview with selected representative examples from the recent literature.