Selective Synthesis and Functionalization of an Acyclic Methylene-Bridged-Arene Trimer in a Cage.

Arene-formaldehyde condensation is a versatile reaction for producing various oligomeric/polymeric materials. However, the precise control of oligomerization degree is still challenging because the starting materials and intermediates have similar reactivities. Here, we demonstrate the selective synthesis of a methylene-bridged arene trimer using the confined cavity of a coordination cage. The limited space of the cavity prevents unregulated polymerization. The confinement effect for the kinetic protection is also demonstrated by the subsequent site-selective iodination of the trimer product within the cage.

Chemical Site-Differentiation of Calix[4]arenes through Enforced Conformations by Confinement in a Cage.

Desymmetrization of a symmetric skeleton enables late-stage functionalization of molecules. However, reagent-controlled desymmetrization by site-selective reactions of symmetric molecules remains a difficult synthetic strategy. Here, we found that complete confinement of a symmetric molecule within a coordination cage can desymmetrize the guest conformation, making it possible to site-selectively activate or protect the otherwise equivalent reaction sites of calix[4]arene derivatives. Multistep, one-cage reactions also demonstrated the transformation of an AAAA-type calix[4]arene into a lower symmetry ABAC-type one.

Tetradehydro-Diels-Alder Reactions of Flexible Arylalkynes via Folding Inside a Molecular Cage.

The tetradehydro-Diels-Alder (TDDA) reaction is a useful transformation for the rapid assembly of polycyclic scaffolds from simple linear precursors in a single synthetic step. However, the reaction requires careful substrate design and harsh reaction conditions to overcome the inherent entropic cost for this transformation. Herein we report an efficient site-selective TDDA transformation within a self-assembled Pd6L4 cage. Despite the large size, the flexibility of the employed substrates allows for efficient encapsulation within the host cavity. The rate of thermal cyclization of the encapsulated guest was found to be greatly enhanced, and high product selectivity for an unsymmetrical substrate was observed. The efficiency of this system relies on the precise conformational control of the substrate within the confined space of the host cage.

Synthetic Modulation of an Unstable Dehydrosecodine-type Intermediate and Its Encapsulation into a Confined Cavity Enable Its X-ray Crystallographic Observation.

Numerous indole alkaloids such as the iboga- and aspidosperma-type are believed to be biosynthesized via a common hypothetical intermediate, dehydrosecodine. The highly reactive nature of dehydrosecodine-type compounds has hampered their isolation and structural elucidation. In this study, we achieved the first X-ray structural determination of a dehydrosecodine-type compound by integrating synthetic optimization of the reactivity and stabilizing the fragile molecule by encapsulation into a supramolecular host. Formation of a 1 : 1 complex of the dehydrosecodine-type labile guest bearing both vinyl indole and dihydropyridine units with the host was observed. This integrated approach not only provides insights into the biosynthetic conversions but also allows stabilization and storage of the reactive and otherwise short-lived intermediate within the confined hydrophobic cavity.

A self-assembled coordination cage enhances the reactivity of confined amides via mechanical bond-twisting.

Self-assembled coordination cages composed of metal cations and ligands can enhance the hydrolysis of non-covalently trapped amides in mild conditions as demonstrated in recent experiments. Here, we reveal the mechanism that accelerates base-catalyzed amide hydrolysis inside the octahedral coordination cage, by means of a quantum mechanics/molecular mechanics/polarizable continuum model. The calculated activation barrier of the nucleophilic OH- addition to a planar diaryl amide drastically decreases in the cage because of mechanical bond-twisting due to host-guest π-stacking. By contrast, the OH- addition to an N-acylindole, which possesses a twisted amide bond in bulk water, is not enhanced in the cage. Even though the cage hinders OH- collisions with the confined amide, the cage can twist the dihedral angle of the planar amide so as to mimic the transition state of OH- addition.

Selective Confinement of Rare-Earth-Metal Hydrates by a Capped Metallo-Cage under Aqueous Conditions.

The properties of rare-earth-metal ions in aqueous media often depend on their various hydration modes, which allow them to exist as monomeric or oligomeric species with different coordination numbers. Capturing rare-earth-metal ions in a confined cavity can fix their hydration modes and thus enable their intrinsic properties to be distinguished. However, the isolation of ionic species from bulk aqueous media is not an easy task due to competitive interaction with bulk water. Here, we report the encapsulation of hydrated rare-earth-metal ions in a hydrophobic cavity of a synthetic cage. Cap-like counter anions located at the cage's portals play an important role in capturing the rare-earth metals at a fixed position via electrostatic interactions. Preferential encapsulation of early lanthanoid (III) ions was observed even though all the rare-earth metals have the same hydration number and geometry, as visualized by the competitive inclusion of a dye molecule. Accordingly, the early lanthanoid ion was selectively extracted from a mixture of two rare-earth-metal ions.

Electrophilic Spirocyclization of a 2-Biphenylacetylene via Conformational Fixing within a Hollow-Cage Host.

A 2-biphenylacetylene was fixed into a specific conformation within the confined cavity of a hollow cage, where it underwent a regioselective spirocyclization in the presence of an electrophile. A 5-endo-dig cyclization proceeded selectively in the cage, which stands in sharp contrast to the 6-endo-dig cyclization that normally occurs in common organic media. The folded conformation adopted by the substrate within the cage was examined by 1 H NMR spectroscopy and X-ray crystallographic analysis.

An Ir3L2 complex with anion binding pockets: photocatalytic E-Z isomerization via molecular recognition.

A molecular host with photosensitizing centers provides photo-responsive host-guest properties based on its molecular recognition ability. Here, we construct a self-assembled photoactive Ir(iii) cage-shaped complex that contains anion binding pockets on its rim. The anion recognition ability of the complex enables efficient catalysis of the visible-light-induced E-Z isomerization of an anionic styrene derivative.

Confinement of Water-Soluble Cationic Substrates in a Cationic Molecular Cage by Capping the Portals with Tripodal Anions.

The ability of a cationic coordination cage to encapsulate molecular guests is enhanced by non-covalent capping of the cage portals with tripodal anions. The capped cage provides new cation binding sites at the portals, which enable accommodation of cationic substrates within the cationic cage. In addition, non-covalent capping allows neutral guests in the cage to be exchanged for cationic ones on demand.

Effect of the Thermal Boundary Resistance in Metal/Dielectric Thermally Conductive Layers on Power Generation of Silicon Nanowire Microthermoelectric Generators.

In microthermoelectric generators (µTEGs), parasitic thermal resistance must be suppressed to increase the temperature difference across thermocouples for optimum power generation. A thermally conductive (TC) layer is typically used in µTEGs to guide the heat flow from the heat source to the hot junction of each thermocouple. In this study, we investigate the effect of the thermal boundary resistance (TBR) in metal/dielectric TC layers on the power generation of silicon nanowire (SiNW) µTEGs. We prepared various metal/adhesion/dielectric TC layers using different metal, adhesion, and dielectric layers and measured the thermal resistance using the frequency-domain thermoreflectance method. We found that the thermal resistance was significantly different, mainly due to the TBR of the metal/dielectric interfaces. Interface characterization highlights the significant role of the interfacial bonding strength and interdiffusion in TBR. We fabricated a prototype SiNW-µTEG with different TC layers for testing, finding that the power generation increased significantly when the thermal resistance of the TC layer was lowered. This study helps to understand the underlying physics of thermal transport at interfaces and provides a guideline for the design and fabrication of µTEGs to enhance power generation for effective energy harvesting.

Enhanced reactivity of twisted amides inside a molecular cage.

When an amide group is distorted from its planar conformation, the conjugation between the nitrogen lone pair and the π* orbital of the carbonyl is disrupted and the reactivity towards nucleophiles is enhanced. Although there are several reports on the synthesis of activated twisted amides, amide activation through mechanical twisting is much less common. Here, we report twisted amides that are stabilized through their inclusion in a self-assembled coordination cage. When secondary aromatic amides are included in a Td-symmetric cage, the cis-twisted conformation is favoured over the trans-planar one-as evidenced by single-crystal X-ray diffraction analysis-revealing that the amide can twist by up to 34°. As a consequence of this distortion, the hydrolysis of amides is significantly accelerated upon inclusion.

Effect of Thermal Boundary Resistance between the Interconnect Metal and Dielectric Interlayer on Temperature Increase of Interconnects in Deeply Scaled VLSI.

Temperature increase in the continuously narrowing interconnects accelerates the performance and reliability degradation of very large scale integration (VLSI). Thermal boundary resistance (TBR) between an interconnect metal and dielectric interlayer has been neglected or treated approximately in conventional thermal analyses, resulting in significant uncertainties in performance and reliability. In this study, we investigated the effects of TBR between an interconnect metal and dielectric interlayer on temperature increase of Cu, Co, and Ru interconnects in deeply scaled VLSI. Results indicate that the measured TBR is significantly higher than the values predicted by the diffuse mismatch model and varies widely from 1 × 10-8 to 1 × 10-7 m2 K W-1 depending on the liner/barrier layer used. Finite element method simulations show that such a high TBR can cause a temperature increase of hundreds of degrees in the future VLSI interconnect. Characterization of interface properties shows the significant importance of interdiffusion and adhesion in TBR. For future advanced interconnects, Ru is better than Co for heat dissipation in terms of TBR. This study provides a guideline for the thermal management in deeply scaled VLSI.

A Double-Walled Knotted Cage for Guest-Adaptive Molecular Recognition.

We synthesized a double-walled knotted cage from a flexible tripodal ligand. The characteristic double-walled structure provided a unique adaptive behavior of the cavity upon inclusion of organic molecules, which was evidenced by NMR and X-ray measurements. The semiflexible host framework, restricted by the knotted topology, enabled kinetic molecular recognition revealing the sequential binding of two different guests from their mixture.

Demethylenation of Cyclopropanes via Photoinduced Guest-to-Host Electron Transfer in an M6 L4 Cage.

Unusual demethylenation reactions of cyclopropanes under UV-light irradiation were found within a cavity of a photoactive coordination cage. The reaction proceeded via a guest-to-host electron transfer owing to the highly electron-deficient nature of the cage. The reactions were highly chemoselective and enabled late-stage derivatization of a steroid molecule, which led to a totally new un-natural steroid.

Site-Selective Functionalization of Linear Diterpenoids through U-Shaped Folding in a Confined Artificial Cavity.

Even flexible linear substrates are conformationally fixed within the hydrophobic confined cavities of enzymes. This enables preorganization of the substrates and their positioning in close proximity to the active center to facilitate stereo- and site-selective reactions. Here, we demonstrate the site-selective electrophilic addition of linear diterpenoids within a self-assembled coordination cage. The reactions proceed through folding of the linear substrates into a U-shaped conformation, which results in noncovalent protection of internal C═C bonds to enhance the site selectivity.

Miniaturized planar Si-nanowire micro-thermoelectric generator using exuded thermal field for power generation.

For harvesting energy from waste heat, the power generation densities and fabrication costs of thermoelectric generators (TEGs) are considered more important than their conversion efficiency because waste heat energy is essentially obtained free of charge. In this study, we propose a miniaturized planar Si-nanowire micro-thermoelectric generator (SiNW-µTEG) architecture, which could be simply fabricated using the complementary metal-oxide-semiconductor-compatible process. Compared with the conventional nanowire µTEGs, this SiNW-µTEG features the use of an exuded thermal field for power generation. Thus, there is no need to etch away the substrate to form suspended SiNWs, which leads to a low fabrication cost and well-protected SiNWs. We experimentally demonstrate that the power generation density of the SiNW-µTEGs was enhanced by four orders of magnitude when the SiNWs were shortened from 280 to 8 µm. Furthermore, we reduced the parasitic thermal resistance, which becomes significant in the shortened SiNW-µTEGs, by optimizing the fabrication process of AlN films as a thermally conductive layer. As a result, the power generation density of the SiNW-µTEGs was enhanced by an order of magnitude for reactive sputtering as compared to non-reactive sputtering process. A power density of 27.9 nW/cm2 has been achieved. By measuring the thermal conductivities of the two AlN films, we found that the reduction in the parasitic thermal resistance was caused by an increase in the thermal conductivity of the AlN film and a decrease in the thermal boundary resistance.

Cavity-Directed Chromism of Phthalein Dyes.

Phthalein dyes in the quinone dianion form (pseudo-D3, colored) are transformed into the lactone dianion form (pseudo-T(d), colorless) through encapsulation in a T(d)-symmetric host even under basic conditions (pH ∼10). The compatibility in size and symmetry between the lactone and the cavity is essential to the transformation. Upon addition of a guest that strongly binds to the cavity, the encapsulated phenolphthalein is expelled, the color of the basic solution is regained, and the host-guest complexation is thus visualized.

Halogen-Bond-Assisted Guest Inclusion in a Synthetic Cavity.

The confined space inside a self-assembled cage enhanced halogen bonding (XB) between iodoperfluorocarbons (XB donors) and NO3(-) anions or H2O molecules (XB acceptors), as confirmed by NMR spectroscopy in solution and by X-ray crystallography in the solid state. The cavity also bound an XB donor-acceptor pair, C6F3I3 and C6H5NMe2, in a selective pairwise fashion.

Recognition of polyfluorinated compounds through self-aggregation in a cavity.

Polyfluorinated aliphatic compounds were encapsulated by a self-assembled M6L4 coordination host in aqueous media. NMR titration and X-ray crystallographic analyses clearly revealed that the aggregation of the fluorinated moieties of the guests in the host cavity plays a significant role in the binding. Polyfluorinated aromatics did not show such aggregation in the cavity because of their "nonfluorous" nature.

Temporary and permanent trapping of the metastable twisted conformer of an overcrowded chromic alkene via encapsulation.

An overcrowded alkene with an anti-folded conformation was converted to its twisted conformer, accompanied by a dramatic color change from yellow to deep purple, by inclusion in a self-assembled T(d)-symmetric coordination cage. The shape of the caged cavity was suitable and desirable for trapping of the twisted conformer. The twisted conformation was temporarily memorized in the alkene even after guest ejection. Permanent trapping of the twisted conformation was achieved by bromination of the twisted conformer formed in situ in the cage.