From Biomass to Functional Crystalline Diamond Nanothread: Pressure-Induced Polymerization of 2,5-Furandicarboxylic Acid.

2,5-Furandicarboxylic acid (FDCA) is one of the top-12 value-added chemicals from sugar. Besides the wide application in chemical industry, here we found that solid FDCA polymerized to form an atomic-scale ordered sp3-carbon nanothread (CNTh) upon compression. With the help of perfectly aligned π-π stacked molecules and strong intermolecular hydrogen bonds, crystalline poly-FDCA CNTh with uniform syn-configuration was obtained above 11 GPa, with the crystal structure determined by Rietveld refinement of the X-ray diffraction (XRD). The in situ XRD and theoretical simulation results show that the FDCA experienced continuous [4 + 2] Diels-Alder reactions along the stacking direction at the threshold C···C distance of ∼2.8 Å. Benefiting from the abundant carbonyl groups, the poly-FDCA shows a high specific capacity of 375 mAh g-1 as an anode material of a lithium battery with excellent Coulombic efficiency and rate performance. This is the first time a three-dimensional crystalline CNTh is obtained, and we demonstrated it is the hydrogen bonds that lead to the formation of the crystalline material with a unique configuration. It also provides a new method to move biomass compounds toward advanced functional carbon materials.

Xenon Induces Its Own Preferred Heterochiral Host from Exclusive Homochiral Assembly.

Xenon binding represents a formidable challenge, and efficient hosts remain rare. Here we report our findings that while enantiomeric bis(urea)-bis(thiourea) macrocycles form exclusive homochiral dimeric assemblies, xenon is able to overcome the narcissism and induces an otherwise-nonobservable heterochiral assembly as its preferred host. An experimental approach and fitting model were developed to obtain binding constants associated with the invisible assembly species. The determined xenon binding affinity with the heterochiral capsule reaches 1600 M-1, which is 15 times higher than that with the homochiral capsule and represents the highest record for an assembled host. The origin of the large difference in xenon affinity between the two subtle diastereotopic assemblies was revealed by single-crystal analysis. In the heterochiral capsule with S4 symmetry, the xenon atom is more tightly enclosed by van der Waals surroundings of the four thiourea groups arranged in a spherical cross-array, superior to the antiparallel array in the homochiral capsule with D2 symmetry.

Rhodium-Catalyzed ON-OFF Switchable Hydrogenation Using a Molecular Shuttle Based on a [2]Rotaxane with a Phosphine Ligand.

A novel pH-responsive molecular shuttle based on a [2]rotaxane with a phosphine ligand has been designed and synthesized. In the rhodium-catalyzed hydrogenation of α,ß-dehydroamino acid esters and aryl enamides, ON/OFF-switchable catalysis was accomplished with high ON/OFF ratios by adjusting the movements of the rotaxane wheels located at the catalyst terminals with acid/base. Mechanistic studies using NMR spectroscopy and quasi in situ X-ray photoelectron spectroscopy revealed that RhIII -hydride species are possibly formed in a H2 atmosphere when the catalyst is in the OFF state. During the reaction, a heterolytic activation of dihydrogen occurs by the interlocked rotaxane dibenzylamine and RhI catalytic center acting as a frustrated Lewis pair. Subsequent homolytic splitting of dihydrogen with the newly formed RhI -hydride species generates RhIII -hydride species. These findings show that a substrate-selective hydrogenation can be achieved by using the OFF-state catalyst.

Bioinspired Crowding Inhibits Explosive Ice Growth in Antifreeze Protein Solutions.

Antifreeze (glyco)proteins (AF(G)Ps) are naturally evolved ice inhibitors incomparable to any man-made materials, thus, they are gaining intensive interest for cryopreservation and beyond. AF(G)Ps depress the freezing temperature (Tf) noncolligatively below the melting temperature (Tm), generating a thermal hysteresis (TH) gap, within which the ice growth is arrested. However, the ice crystals have been reported to undergo a retaliatory and explosive growth beyond the TH gap, which is lethal to living organisms. Although intensive research has been carried to inhibit such an explosive ice growth, no satisfactory strategy has been discovered until now. Here, we report that crowded solutions mimicking an extracellular matrix (ECM), in which AF(G)Ps are located, can completely inhibit the explosive ice growth. The crowded solutions are the condensates of liquid-liquid phase separation consisting of polyethylene glycol (PEG) and sodium citrate (SC), which possess a nanoscale network and strong hydrogen bond (HB) forming ability, completely different to crowded solutions made of single components, that is, PEG or SC. Due to these unique features, the dynamics of the water is significantly slowed down, and the energy needed for breaking the HB between water molecules is distinctly increased; consequently, ice growth is inhibited as the rate of water molecules joining the ice is substantially reduced. The present work not only opens a new avenue for cryopreservation, but also suggests that the ECM of cold-hardy organisms, which also exhibit great water confining properties, may have a positive effect in protecting the living organisms from freezing damage.

Regulating the Structures of Self-Assembled Mechanically Interlocked Moleculecular Constructs via Dianion Precursor Substituent Effects.

Substituent effects play critical roles in both modulating reaction chemistry and supramolecular self-assembly processes. Using substituted terephthalate dianions (p-phthalic acid dianions; PTADAs), the effect of varying the type, number, and position of the substituents was explored in terms of their ability to regulate the inherent anion complexation features of a tetracationic macrocycle, cyclo[2](2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene) (referred to as the Texas-sized molecular box; 14+), in the form of its tetrakis-PF6- salt in DMSO. Several of the tested substituents, including 2-OH, 2,5-di(OH), 2,5-di(NH2), 2,5-di(Me), 2,5-di(Cl), 2,5-di(Br), and 2,5-di(I), were found to promote pseudorotaxane formation in contrast to what was seen for the parent PTADA system. Other derivatives of PTADA, including those with 2,3-di(OH), 2,6-di(OH), 2,5-di(OMe), 2,3,5,6-tetra(Cl), and 2,3,5,6-tetra(F) substituents, led only to so-called outside binding, where the anion interacts with 14+ on the outside of the macrocyclic cavity. The differing binding modes produced by the choice of PTADA derivative were found to regulate further supramolecular self-assembly when the reaction components included additional metal cations (M). Depending on the specific choice of PTADA derivatives and metal cations (M = Co2+, Ni2+, Zn2+, Cd2+, Gd3+, Nd3+, Eu3+, Sm3+, Tb3+), constructs involving one-dimensional polyrotaxanes, outside-type rotaxanated supramolecular organic frameworks (RSOFs), or two-dimensional metal-organic rotaxane frameworks (MORFs) could be stabilized. The presence and nature of the substituent were found to dictate which specific higher order self-assembled structure was obtained using a given cation. In the specific case of the 2,5-di(OH), 2,5-di(Cl), and 2,5-di(Br) PTADA derivatives and Eu3+, so-called MORFs with distinct fluorescence emission properties could be produced. The present work serves to illustrate how small changes in guest substitution patterns may be used to control structure well beyond the first interaction sphere.

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.

Excimer Disaggregation Enhanced Emission: A Fluorescence "Turn-On" Approach to Oxoanion Recognition.

A new approach to anion sensing that involves excimer disaggregation induced emission (EDIE) is reported. It involves the anion-mediated disaggregation of the excimer formed from a cationic macrocycle. This leads to an increase in the observed fluorescence intensity. The macrocycle in question, cyclo[1] N2, N6-dimethyl- N2, N6-bis(6-(1 H-imidazolium-1-yl)pyridin-2-yl)pyridine-2,6-diamine[1]1,4-dimethylbenzene (12+; prepared as its PF6- salt), is obtained in ca. 70% yield via a simple cyclization. X-ray diffraction analyses of single crystals revealed that, as prepared, this macrocycle exists in a supramolecular polymeric form in the solid state. Macrocycle 12+ is weakly fluorescent in acetonitrile. The emission intensity is concentration dependent, with the maximum intensity being observed at [12+] ≈ 0.020 mM. This finding is ascribed to formation of an excimer, followed possibly by higher order aggregates as the concentration of 12+ is increased. Addition of tetrabutylammonium pyrophosphate (HP2O73-) to 12+ (0.020 mM in acetonitrile) produces a ca. 200-fold enhancement in the emission intensity (λex = 334 nm; λem = 390-650 nm). These findings are rationalized in terms of the HP2O73- serving to break up essentially non-fluorescent excited-state dimers of 12+ through formation of a highly fluorescent anion-bound monomeric complex, 12+·HP2O73-. A turn-on in the fluorescence intensity is also seen for H2PO4- and, to a lesser extent, HCO3-. Little (HSO4-, NO3-) or essentially no (N3-, SCN-, F-, Cl-, Br- and I-) response is seen for other anions. Solid-state structural analysis of single crystals obtained after treating 12+ with HP2O73- in the presence of water revealed a salt form wherein a H2P2O72- anion sits above the cone-like macrocycle.

From CO2 to 4 H-Quinolizin-4-ones: A One-Pot Multicomponent Approach via Ag2O/Cs2CO3 Orthogonal Tandem Catalysis.

Using carbon dioxide as a C1 precursor, here we report relatively simple and cost-effective orthogonal tandem catalysis, namely Ag2O in conjunction with Cs2CO3 serves to promote a multicomponent tandem reaction forming two new C-C and one new C-N bonds. 4 H-Quinolizin-4-ones, key skeletal components in a variety of biologically active molecules, were obtained with yields up to 99%. The present approach features a broad substrate scope and mild reaction conditions and benefits from using cost-effective reaction and catalysts.

Directional Molecular Transportation Based on a Catalytic Stopper-Leaving Rotaxane System.

Ratchet mechanism has proved to be a key principle in designing molecular motors and machines that exploit random thermal fluctuations for directional motion with energy input. To integrate ratchet mechanism into artificial systems, precise molecular design is a prerequisite to control the pathway of relative motion between their subcomponents, which is still a formidable challenge. Herein, we report a straightforward method to control the transportation barrier of a macrocycle by selectively detaching one of the two stoppers using a novel DBU-catalyzed stopper-leaving reaction in a rotaxane system. The macrocycle was first allowed to thread onto a semidumbbell axle from the open end and subsequently thermodynamically captured into a nonsymmetrical rotaxane. Then, it was driven energetically uphill until it reached a kinetically trapped state by destroying its interaction with ammonium site, and was finally quantitatively released from the other end when the corresponding stopper barrier was removed. Although the directional transportation at the present system was achieved by discrete chemical reactions for the sake of higher transportation efficiency, it represents a new molecular transportation model by the strategy of using stopper-leavable rotaxane.

Self-Assembly of a [2]Pseudorotaxane by an Inchworm-Motion Mechanism.

The threading of biomolecules through pores or channels in membranes is important to validate the physiological activities of cells. To aid understanding of the controlling factors required for the translocation in space with confined size and distorted conformation, it is desirable to identify experimental systems with minimized complexity. We demonstrate the mechanism of a linear guest L1 threading into a tris(crown ether) host TC with a combinational distorted cavity to form a triply interlocked [2]pseudorotaxane 3in-[L1⊂TC]. An inchworm-motion mechanism is proposed for the process. For the forward-threading steps that lead to the formation of higher-order interlocked species, guest L1 must adopt a bent conformation to find the next crown ether cavity. Two simplified models are applied to investigate the self-assembly dynamic of 3in-[L1⊂TC]. Kinetic NMR spectroscopic and molecular dynamics (MD) studies show that formation of the singly penetrated species is fast, whereas formation of the doubly and triply threaded species is several orders of magnitude slower. During threading the freedom of both the guest L1 and host TC gradually decrease due to their interactions. This results in a significant entropy effect for the threading dynamic, which is also observed for the threading of a biomolecular chain through a channel.

Stabilizing G-quadruplex DNA by methylazacalix[n]pyridine through shape-complementary interaction.

It is found that G-quadruplexes have important functions in biological systems, such as gene expression. Molecules which can stabilize the G-quadruplex structure may have potential application in regulating the expression of gene. A series of methylazacalix[n]pyridine (n=4, 6, 7, 8, 9) has been tested to stabilize the intermolecular human telomeric G-quadruplex (T12 and H12), intramolecular TBA, c-kit and bcl-2 G-quadruplex by CD denaturation experiments. The results showed that only methylazacalix[6]pyridine (MACP6) can stabilize the intermolecular G-quadruplex formed from the 12bp human telomere. Further studies evidenced that the shape-complementary binding mode was what contributed to the interaction between MACP6 and T12 G-quadruplex.

Stepwise Motion in a Multivalent [2](3)Catenane.

The motions of biomolecular machines are usually multistep processes, and are involved in a series of conformational changes. In this paper, a novel triply interlocked [2](3)catenane composed of a tris(crown ether) host eTC and a circular ditopic guest with three dibenzyl ammonium (DBA) sites and three N-methyltriazolium (MTA) sites was reported. Due to the multivalency nature of the catenane, the acid-base triggered motion was performed by a stepwise manner. The coconformations of the four related stable states have been directly identified and quantified which confirmed the multistep process. In order to quantify the dynamics with environmental acidity changes, the values of the three levels of dissociation constant pKa have been determined. The special interlocked topology of the [2](3)catenane also endows the motion of each crown ether ring in the host with unexpected selectivity for the MTA sites. This study provides clues to comprehend the underlying motion mechanism of intricate biological molecular machines, and further design artificial molecular machine with excellent mechanochemistry properties.

Multicomponent Self-Assembled Metal-Organic [3]Rotaxanes.

A set of environmentally responsive metal-organic [3]rotaxanes is described. These mechanically interlocked macromolecules may be prepared in quantitative yield via a one-pot procedure involving treatment of a flexible tetracationic macrocycle, known as the Texas-sized molecular box, with tri-1,3,5-benzenetricarboxylate anion and silver cations (Ag(+)). The use of this three-component mixture gives rise to a metal-organic [3]rotaxane via a self-assembly process that occurs under ambient conditions in DMSO-d6 solution. The complex is stable in the presence of excess TFA. However, disassembly of the [3]rotaxane to produce anion-box associated entities may be triggered by adding a competitive counteranionic species (e.g., I(-)). Adding excess Ag(+) serves to reverse this decomplexation process. The nature of the [3]rotaxane complex could be fine-tuned via application of an external stimulus. Increasing the temperature or adding small molecules (e.g., D2O, methanol-d4, acetonitrile-d3, DMF-d7, acetone-d6, or THF-d8) to the initial DMSO-d6 solution induces conformational flipping of the macrocycle within the overall complex (e.g., from limiting chair to chairlike forms). Support for the molecular stimuli responsive nature of the various structures came from solution-phase one- and two-dimensional ((1)H, 1D and 2D NOESY) NMR spectroscopic studies carried out in DMSO-d6. The core metal-linked rotaxane unit was characterized via single-crystal X-ray diffraction analysis. Initial evidence that the present self-assembly process is not limited to the use of the Ag(+) cation came from studies involving Cd(2+); this replacement results in formation of 2D metal-organic rotaxane-containing frameworks (MORFs).

G4LDB: a database for discovering and studying G-quadruplex ligands.

The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800 G-quadruplex ligands with ∼4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.

Cation-triggered switchable asymmetric catalysis with chiral Aza-CrownPhos.

An aza-crown ether, modified phosphoramidite ligand, has been designed and synthesized. The ON/OFF reversible switch of catalytic activity for its rhodium catalyst was thoroughly investigated in the asymmetric hydrogenation of dehydroamino acid esters modulated by host-guest interactions. In the OFF state, the catalyst is almost inactive (less than 1% conversion) because of the formation of an intermolecular sandwich complex by two aza-crown ether moities and the cationic rhodium metal center. In using alkali-metal-cations as the trigger, the catalytic activity was turned ON and consequently resulted in full conversions and excellent enantioselectivities (up to 98% ee).

Controlled interconversion of macrocyclic atropisomers via defined intermediates.

Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C2v and C4v symmetry denoted as C2v-OC-4 and C4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C2v- to C4v-OC-4 via a Cs-symmetric intermediate (Cs-OC-4). It differs from the typical transition state-mediated processes of simple C-C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C2v- and Cs-OC-4 from C4v-OC-4. In contrast to C2v-OC-4, C4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations.

Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.

Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes. Moreover, the binding and releasing of the guests in the complexes could be controlled by potassium ions.

Thermally-induced atropisomerism promotes metal-organic cage construction.

Molecular folding regulation with environmental stimuli is critical in living and artificial molecular machine systems. Herein, we described a macrocycle, cyclo[4] (1,3-(4,6-dimethyl)benzene)[4](1,3-(4,6-dimethyl)benzene)(4-pyridine). Under 298 K, it has three stable stiff atropisomers with names as 1 (Cs symmetry), 2 (Cs symmetry), and 3 (C4v symmetry). At 393 K, 1 can reversibly transform into 2, but at 473 K, it can irrevocably transform into 3. At 338 K, 3 and (PhCN)2PdCl2 complex to produce the metal-organic cage 4. Only at 338 K does the combination of 1 or 2 and (PhCN)2PdCl2 create a gel-like structure. Heating both gels to 473 K transforms them into 4. In addition to offering a thermally accelerated method for modifying self-assembled systems using macrocyclic building blocks, this study also has the potential to develop the nanoscale transformation material with a thermal response.

Stabilizing G-quadruplex DNA by a scissors-shaped binaphthyl derivative through the entangling mode: cooperation of binaphthylene and the ethoxy chain.

A scissors-shaped binaphthyl derivative (NPA) has been found to stabilize the G-quadruplex by intertwisting the whole G-quadruplex with two long chains, through the cooperation of the two functional groups: binaphthylene and the ethoxy chain. Moreover, NPA exhibits a good inhibitory effect of telomerase activity as well as excellent cytotoxic activity against HepG-2 human liver cancer cells.

Planar quinary cluster inside a fullerene cage: synthesis and structural characterizations of Sc(3)NC@C(80)-I(h).

The endohedral fullerene Sc(3)NC@C(80)-I(h) has been synthesized and characterized; it has an unprecedented planar quinary cluster in a fullerene cage. It is also the first chemical compound in which the presence of an unprecedented (NC)(3-) trianion has been disclosed. The fascinating intramolecular dynamics in Sc(3)NC@C(80)-I(h) enables the whole molecule to display high polarity and promising ferroelectricity. This finding inspires the possibility that such a planar quinary cluster may be useful in constructing many other endohedral fullerenes.