Reengineering of an Artificial Protein Cage for Efficient Packaging of Active Enzymes.

Protein cages that readily encapsulate active enzymes of interest present useful nanotools for delivery and catalysis, wherein those with programmable disassembly characteristics serve as particularly attractive platforms. Here, a general guest packaging system based on an artificial protein cage, TRAP-cage, the disassembly of which can be induced by the addition of reducing agents, is established. In this system, TRAP-cage with SpyCatcher moieties in the lumen is prepared using genetic modification of the protein building block and assembled into a cage structure with either monovalent gold ions or molecular crosslinkers. The resulting protein cage can efficiently capture guest proteins equipped with a SpyTag by simply mixing them in an aqueous solution. This post-assembly loading system, which circumvents the exposure of guests to thiol-reactive crosslinkers, enables the packaging of enzymes possessing a catalytic cysteine or a metal cofactor while retaining their catalytic activity.

Tuning (Photo)Electronic Properties of an Electron Deficient Porous Polymer via n-Doping with Tetrathiafulvalene.

Charge-transfer complex formation within the pores of porous polymers is an efficient way to tune their electronical properties. Introduction of electron accepting guests to the electron donating hosts to conduct their p-doping is intensively studied in this context. However, the vice versa scenario, n-doping by treating the electron deficient (i.e., n-type) porous polymers with electron donating dopants, is rare. In this work, synthesis of an n-type phenazine based conjugated microporous polymer and its exposure to strong electron donating tetrathiafulvalene (TTF) dopants are presented. The fundamental physical characterizations (e.g., elemental analysis, gas sorption) showed that the vacuum impregnation technique is a good approach to load the guest molecules inside the pores. Moreover, the formation of charge-transfer complexes between the phenazine building blocks of the polymeric network and TTF dopants are confirmed via spectral techniques such Fourier transform infra-red, UV-vis, steady-state/time-resolved photoluminescence, and transient absorbance spectroscopies. Effect of the doping to the electronical properties is monitored by employing photoelectrochemical measurements, which showed lower charge-transfer resistivity and nearly doubled photocurrents after the doping. The study is, therefore, an important advancement for the applicability of (n-type) porous polymeric materials in the field of photo(electro)catalysis and organic electronics.

Low Potential CO2 Reduction by Inert Fe(II)-Macrobicyclic Complex: A New Concept of Cavity Assisted CO2 Activation.

The advantage of a pre-organized π-cavity of Fe(II) complex of a newly developed macrobicycle cryptand is explored for CO2 reduction by overcoming the problem of high overpotential associated with the inert nature of the cryptate. Thus, a bipyridine-centered tritopic macrobicycle having a molecular π-cavity capable of forming Fe(II) complex as well as potential for CO2 encapsulation is synthesized. The inert Fe(II)-cryptate shows much lower potential in cyclic voltammetry than the Fe(II)-tris-dimethylbipyridine (Fe-MBP) core. Interestingly, this cryptate shows electrochemical CO2 reduction at a considerably lower potential than the Fe-MBP inert core. Therefore, this study represents that a well-structured π-cavity may generate a new series of molecular catalysts for the CO2 reduction reaction (CO2 RR), even with the inert metal complexes.

Cage Match: Comparing the Anion Binding Ability of Isostructural Versus Isofunctional Pairs of Metal-Organic Nanocages.

Affinities of six anions (mesylate, acetate, trifluoroacetate, p-toluenecarboxylate, p-toluenesulfonate, and perfluorooctanoate) for three related Pt2+ -linked porphyrin nanocages were measured to probe the influence of different noncovalent recognition motifs (e. g., hydrogen bonding, electrostatics, π bonding) on anion binding. Two new hosts of M6 L3 12+ (1b) and M4 L2 8+ (2) composition (M=(en)Pt2+ , L=(3-py)4 porphyrin) were prepared in a one-pot synthesis and allowed comparison of hosts that differ in structure while maintaining similar N-H hydrogen-bond donor ability. Comparisons of isostructural hosts that differ in hydrogen-bonding ability were made between 1b and a related M6 L3 12+ nanoprism (1a, M=(tmeda)Pt2+ ) that lacks N-H groups. Considerable variation in association constants (K1 =1.6×103  M-1 to 1.3×108  M-1 ) and binding mode (exo vs. endo) were found for different host-guest combinations. Strongest binding was seen between p-toluenecarboxylate and 1b, but surprisingly, association of this guest with 1a was only slightly weaker despite the absence of NH⋅⋅⋅O interactions. The high affinity between p-toluenecarboxylate and 1a could be turned off by protonation, and this behavior was used to toggle between the binding of this guest and the environmental pollutant perfluorooctanoate, which otherwise has a lower affinity for the host.

Fluorescence color change of supramolecular polymer networks controlled by crown ether-cation recognition.

We report a fluorescent supramolecular polymer networks (SPNs) system based on crown ether-cation recognition. The polymer side chains bear ammonium cations, which can be recognized by host molecules with a B15C5 unit and a quinoline group at each end. The quinoline group makes the host molecule exhibit blue fluorescence. After the formation of SPNs, the recognition of the crown ether-cation transforms the blue fluorescence into yellow fluorescence. The accompanying fluorescence color change during the formation of SPNs makes it with potential applications in the fields of display, printing, information storage, and bioimaging.

Preferential Formation of Three-layered Host-Guest Complexes of a Planar Dinuclear Metallohost with Alkali Metal Ions.

We synthesized a planar macrocyclic dinuclear nickel(II) metallohost from the corresponding macrocyclic imine ligand containing two N2O2 chelate coordination sites and an O6 cation binding site like 18-crown-6 as well as peripheral hexyl groups. Due to the lipophilic nature of the hexyl groups, the metallohost was soluble in less polar media where its interaction with alkali metal ions was enhanced. The binding studies by NMR spectroscopy clearly showed its strong tendency to form multi-layered structures. The metallohost formed 2:1 and 1:1 (host/guest) complexes with Na+ with the two-step binding constants of logK1 = 6.6 and logK2 = 3.0. In contrast, its complexation with larger alkali metal ions (K+, Rb+, Cs+) preferentially gave 3:2 (host/guest) complexes when 2/3 equiv of the guest was present. The three-layered structures of these 3:2 complexes were well characterized by mass spectrometry and 2D COSY/ROESY experiments as well as DFT calculations, elucidating their unique structural feature with three chemically different environments due to the oppositely curved two [Ni(saloph)] moieties of the metallohost. Therefore, the three-layered structures were preferentially formed when larger alkali metal ions (K+, Rb+, Cs+) were complexed with the metallohost.

Selectivity in Adduct Formation of a Bidentate Boron Lewis Acid.

A bidentate boron Lewis acid based on 1,8-diethynylanthracene has been studied in detail with respect to its adduct formation with diamines and diphosphanes of different linker lengths between the donor functions. A clear correlation between the linker length of the bifunctional base and the formation of 1 : 1 adducts, 1 : 2 adducts or oligomers was found. The adducts were characterized in solution by NMR titration experiments and structurally by X-ray diffraction. In addition, adduct formation and competition experiments of the host system with ZR3 (Z=N, P; R=H, Me) demonstrated the generally higher stability of alkylphosphane adducts compared to alkylamine adducts with boron functions. The results provide a general insight into the adduct formation of bidentate Lewis acids with guests of different sizes as well as the differences in stability between borane-amine and borane-phosphane adducts.

A Study on Auto-Catalysis and Product Inhibition: A Nucleophilic Aromatic Substitution Reaction Catalysed within the Cavity of an Octanuclear Coordination Cage.

The ability of an octanuclear cubic coordination cage to catalyse a nucleophilic aromatic substitution reaction on a cavity-bound guest was studied with 2,4-dinitrofluorobenzene (DNFB) as the guest/substrate. It was found that DNFB undergoes a catalysed reaction with hydroxide ions within the cavity of the cubic cage (in aqueous buffer solution, pH 8.6). The rate enhancement of kcat/kuncat was determined to be 22, with cavity binding of the guest being required for catalysis to occur. The product, 2,4-dinitrophenolate (DNP), remained bound within the cavity due to electrostatic stabilisation and exerts two apparently contradictory effects: it initially auto-catalyses the reaction when present at low concentrations, but at higher concentrations inhibits catalysis when a pair of DNP guests block the cavity. When encapsulated, the UV/Vis absorption spectrum of DNP is red-shifted when compared to the spectrum of free DNP in aqueous solution. Further investigations using other aromatic guests determined that a similar red-shift on cavity binding also occurred for 4-nitrophenolate (4NP) at pH 8.6. The red-shift was used to determine the stoichiometry of guest binding of DNP and 4NP within the cage cavity, which was confirmed by structural analysis with X-ray crystallography; and was also used to perform catalytic kinetic studies in the solution-state.

Borospherene in the Nanohoop: Complexation and Aromaticity of Neutral and Dioxidized Cycloparaphenylene Supramolecules with B40 and C60 Fullerenes.

Supramolecular complexes of carbon nanohoops with fullerenes play a key role for the design of novel nanomaterials with technological applications. Herein we investigate with density functional theory (DFT) methods the capability of neutral and dioxidized cycloparaphenylenes (CPPs) to encapsulate all-boron fullerene B40. Our results show that [9]CPP and [10]CPP are feasible host candidates to encapsulate B40 displaying comparable complexation energies with the all-carbon analog [10]CPP⊃C60. Upon dioxidation the host-guest interactions are not affected, whereas the positive charge is delocalized on the CPPs leading to global aromatic character of the hosts. Consequently, the dicationic complexes [n]CPP2+⊃B40 and [10]CPP2+⊃C60 display augmented global shielding cones that strongly shield the guests, as manifested by large upfield shifts in 11B-NMR and 13C-NMR signals. Hence, CPP complexes with carbon fullerenes can be extended borospherene B40 host-guest complexes, as well as to doubly oxidized species stabilized by global host aromaticity, expanding our understanding of carbon nanohoop complexes to boron-based fullerenes.

para-Phenylenediamine Dimer as a Redox-Active Guest for Supramolecular Systems.

Redox-active components are highly valuable in the construction of molecular devices. We combined two p-phenylenediamines (p-PDA) with a biphenyl (BiPhe) unit to prepare a supramolecular guest 4 consisting of three binding sites for cucurbit[7/8]uril (CBn) and/or cyclodextrins (CD). Supramolecular properties of 4 were investigated using NMR, UV-vis, mass spectrometry and isothermal titration calorimetry. Our analysis revealed that 4 forms higher-order host-guest complexes, wherein a CD unit occupies the central BiPhe site, secured by two CBn units at the terminal p-PDA sites. Additionally, 1 : 1 complexes with α-CD and ß-CD, a 1 : 2 complex with γ-CD and 2 : 1 complexes with CB7 and CB8 were identified. Through UV-vis and cyclic voltammetry, redox processes leading to the formation of a stable, deep blue dication diradical of 4 are elucidated. Furthermore, it is demonstrated that CB7 selectively protects oxidised 4 from reduction in the presence of a reducing agent. The supramolecular and redox properties of the structural motif represented by 4 render it an interesting candidate for the construction of supramolecular devices.

Collective Effects of Multiple Fluorine Atoms Causing π-philic Characteristic within a Caged Polyoxometalate Framework.

Perfluorination brings about distinctive properties arising from the unusual nature of the F element, which have been extensively developed in materials science and chemistry. Herein we report that the construction of F-rich inner space within a hollowed Mo132 O372 cage ([Mo132 O372 (OCOR)30 (H2 O)72 ]42- ) leads to the emergence of unique guest binding activities in encapsulation. Prominently, the trifluoroacetate-modified cage (R=CF3 , 2) having as many as 90 F groups inside favors trapping cyclopentadiene (Cp), which is hardly trapped by the non-fluorinated counterpart (R=CH3 , 1). Systematic studies using related hydrocarbons show that the amount of the encapsulated guest is correlated with the unsaturation degree of the guests, implying the involvement of the attractive interaction of the CF3 -modified interior wall with the guest π-electron clouds. Control experiments using the semi-fluorinated analogues (R=CF2 H, CFH2 ) reveal that the perfluorination is a critical factor to facilitate the Cp encapsulation by 2, indicating that collective effects of polar C-F bonds spreading over the interior surface, rather than the polarity of the individual C-F bonds, are responsible. We also provide a successful example of the physical molecular confinement within the cage through the "ship-in-a-bottle" Diels-Alder reaction between trapped diene and dienophile.

Chameleonic Cages: Encapsulation of Anionic, Neutral, and Cationic Guest Species within [Fe4L4]8+ Tetrahedral Cages Synthesised from the tris(4-aminophenyl)phosphate pro-Ligand.

An adaptable Fe(II) tetrahedral cage, [Fe4L4][BF4]8 (L = tris(4-(((E)-pyridin-2-ylmethylene)amino)phenyl) phosphate), has been synthesised via self-assembly. By modulating the orientation of its pendant P=O groups, the cage was found to be capable of encapsulating anionic, neutral, and cationic guests, which was confirmed in the solid state via single-crystal X-ray diffraction (SCXRD) and in solution by high-resolution mass spectroscopy (HR-MS), as well as by NMR (1H, 19F, 31P) studies where possible.

Construction of Oligorotaxanes with Hydrogen-Bonded Aramide Macrocycles through Threaded Host-Guest Complexation.

The development of efficient and selective organic synthetic approaches for complex molecules has garnered significant attention due to the need for precise control over molecular structures and functions. Rotaxanes, a type of mechanically interlocked molecules (MIMs), have shown promising applications in various fields including sensing, catalysis, and material science. However, the highly selective synthesis of oligo[n]rotaxanes (mostly n≥3) through controlling host-guest complexation and supramolecular threading assembly process still remains an ongoing challenge. In particular, the utilization of two-dimensional (2D) macrocycles with structural shape-persistency for the synthesis of oligo[n]rotaxanes is rare. In this concept, research on cooperatively threaded host-guest complexation with hydrogen-bonded (H-bonded) aramide macrocycles and selective synthetic protocols of oligo[n]rotaxanes has been summarized. The high efficiency and selectivity in synthesis are ascribed to the synergistic interplay of multiple non-covalent bonding interactions such as hydrogen bonding and intermolecular π-π stacking of macrocycles within the unique supramolecular structure of threaded host-guest complexes. This review focuses on the latest progress in the concepts, synthesis, and properties of H-bonded aramide macrocycle-based oligorotaxanes, and presents an in-depth outlook on challenges in this emerging field.

Isomer-Dependent Escape Rate of Xenon from a Water-Soluble Cryptophane Cage Studied by Ab Initio Molecular Dynamics.

The escape of xenon from the anti and syn diastereomers of hexacarboxylic-cryptophane-222 in water has been studied by ab initio molecular dynamics simulations. The structures of both complexes, when the xenon atom is trapped inside their cages, have been compared and show no major differences. The free-energy profiles corresponding to the escape reaction have been calculated with the Blue Moon ensemble method using the distance between Xe and the center of mass of the cage as the reaction coordinate. The resulting free-energy barriers are very different; the escape rate is much faster in the case of the syn diastereomer, in agreement with experimental data obtained in hyperpolarized 129 Xe NMR. Our simulations reveal the mechanistic details for each diastereomer and provide an explanation for the different in-out xenon rates based on the solvation structure around the cages.

Taming XeO3 with Aza-Crowns: Computational Studies into σ-Hole Mediated Host-Guest Interactions.

Various aza-crowns with different sizes and substituents have been explored computationally as potential hosts for stabilizing the explosive guest xenon trioxide (XeO3) through σ-hole-mediated aerogen bonding interactions. Interestingly, aza-crowns demonstrate superior binding towards XeO3 compared to their oxygen and thio counterparts. However, unlike the latter cases, where the binding was found to be increasingly favorable with the increase in the size of the crowns, aza-crowns exhibit a variable size preference for XeO3, peaking with aza-15-crown-5, and reducing thereafter with increase in crown size.

Multi-Hydrogen Bonding on Quaternized-Oligourea Receptor Facilitated Its Interaction with Bacterial Cell Membranes and DNA for Broad-Spectrum Bacteria Killing.

Herein, we report a new strategy for the design of antibiotic agents based on the electrostatic interaction and hydrogen bonding, highlighting the significance of hydrogen bonding and the increased recognition sites in facilitating the interaction with bacterial cell membranes and DNA. A series of quaternary ammonium functionalized urea-based anion receptors were studied. While the monodentate mono-urea M1, bisurea M2, and trisurea M3 failed to break through the cell membrane barrier and thus could not kill bacteria, the extended bidentate dimers D1-D3 presented gradually increased membrane penetrating capabilities, DNA conformation perturbation abilities, and broad-spectrum antibacterial activities against E. coli, P. aeruginosa, S. aureus, E. faecalis, and S. epidermidis.

Polyoxometalate-Organic Hybrid "Calixarenes" as Supramolecular Hosts.

Calixarenes are among the most useful and versatile macrocycles in supramolecular chemistry. The one thing that has not changed in the 80 years since their discovery, despite numerous derivatizations, is their fully organic, covalent scaffolds. Here, we report a new type of organic-inorganic hybrid "calixarenes" constructed by means of coordination-driven assembly. Replacing acetate ligands on the {SiW10 Cr2 (OAc)2 } clusters with 5-hydroxyisophthalates allows these 95° inorganic building blocks to be linked into bowl-shaped, hybrid "calix[n]arenes" (n=3, 4). With a large concave cavity, the metal-organic calix[4]arene can accommodate nanometer-sized polyoxoanions in an entropically driven process. The development of hybrid variants of calixarenes is expected to expand the scope of their physicochemical properties, guest/substrate binding, and applications on multiple fronts.

2,3 : 6,7-Naphthalene Bis(dicarboximide) Cyclophane: A Photofunctional Host for Ambient Delayed Fluorescence in Solution.

Harvesting triplet excitons of heavy atom-free purely organic chromophores under aerated conditions is challenging due to the quenching of long-lived triplet states by molecular oxygen and vibrational dissipation. Herein, we show a supramolecular approach of triplet harvesting via mitigating quenching pathways of a triplet harvester. Specifically, we used a host-guest system based on 2,3 : 6,7-naphthalene bis(dicarboximide)-derived cyclophane (NBICy) and carbazole derivative (EtCz). Complexation studies and single-crystal X-ray analysis showed the formation of a rigid host-guest complex (K≈104 M-1 in CCl4), resulting in triplet-exciton stabilization under aerated conditions via mitigating vibrational interference and oxygen quenching. Photophysical studies elucidate the delayed fluorescence emission from the charge-transfer state (1CT) with a quantum yield (QY) of 6-8 % under ambient conditions which increased up to 36 % in an inert atmosphere.

A Conjugated Phenylene Nanocage with a Guest-Adaptive Deformable Cavity.

The highly strained, phenylene-derived organic cages are typically regarded as very rigid entities, yet their deformation potential and supramolecular properties remain underexplored. Herein, we report a pliable conjugated phenylene nanocage by synergistically merging rigid and flexible building blocks. The anisotropic cage molecule contains branched phenylene chains capped by a calix[6]arene moiety, the delicate conformational changes of which endow the cage with a remarkably deformable cavity. When complexing with fullerene guests, the cage showcases excellent guest-adaptivity, with its cavity volume capable of swelling by as much as 85 %.

Room-Temperature Near-Infrared Phosphorescence from C64 Nanographene Tetraimide by π-Stacking Complexation with Platinum Porphyrin.

Near-Infrared (NIR) phosphorescence at room temperature is challenging to achieve for organic molecules due to negligible spin-orbit coupling and a low energy gap leading to fast non-radiative transitions. Here, we show a supramolecular host-guest strategy to harvest the energy from the low-lying triplet state of C64 nanographene tetraimide 1. 1H NMR and X-ray analysis confirmed the 1 : 2 stoichiometric binding of a Pt(II) porphyrin on the two π-surfaces of 1. While the free 1 does not show emission in the NIR, the host-guest complex solution shows NIR phosphorescence at 77 K. Further, between 860-1100 nm, room temperature NIR phosphorescence (λmax=900 nm, τavg=142 µs) was observed for a solid-state sample drop-casted from a preformed complex in solution. Theoretical calculations reveal a non-zero spin-orbit coupling between isoenergetic S1 and T3 of π-stacked [1 ⋅ Pt(II) porphyrin] complex. External heavy-atom-induced spin-orbit coupling along with rigidification and protection from oxygen in the solid-state promotes both the intersystem crossing from the first excited singlet state into the triplet manifold and the NIR phosphorescence from the lowest triplet state of 1.