Tröger's Base-Based Cuboid Constructed by Chiral Self-Discrimination.

Cuboid, a basic geometric structure, has been widely applied in architecture and mathematics. In chemistry, the introduction of cuboid structures always provides a specific structural shape, enhances the stability of the structure and improves the performance of materials. Herein, a simple strategy exploiting self-discrimination to construct a cuboid-stacking crystal material is proposed, in which a chiral macrocycle (TBBP) based on Tröger's base (TB) and benzophenone (BP) was synthesized as the building element of the cuboid. The cuboid is designed to be transformable compared with cuboid structures in previous work. For this reason, it is considered that the cuboid-stacking structure can be transformed through external stimulation. Iodine vapor is selected as the external stimulus to transform the cuboid-stacking structure due to the favorable interaction between iodine and the cuboid. The changes in the stacking mode of TBBP is studied by single-crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD). To our surprise, this Tröger's base-based cuboid shows strong iodine adsorption capacity up to 3.43 g g-1 and exhibits potential as a crystal material for iodine adsorption.

Effective Iodine Capture Behavior by a Censer-shaped Macrocycle in Vapor Phase and Aqueous Solution.

Iodine capture is of great significance for disposal of the hazardous radioactive iodine. CTX[P(O)Ph], one kind of censer-shaped macrocycle cyclotrixylohydroquinoylene (CTX) derivatives, was applied as an efficient iodine adsorbent. It showed satisfactory iodine adsorption capacity in vapor phase and could be reused without obvious adsorption capacity loss. Besides, the adsorbent could also uptake iodine in water. Fortunately, two iodine loading CTX[P(O)Ph] crystal structures were obtained under different conditions to explore the mechanism of iodine adsorption. This work provides a relatively rare example of iodine adsorption by macrocycle. It is promising that the results with crystal information might be meaningful for exploring and designing new kinds of iodine adsorbents.

The Preparation of a Water-Soluble Phospholate-Based Macrocycle for Constructing Artificial Light-Harvesting Systems.

On the basis of cyclotrixylohydroquinoylene (CTX), a novel water-soluble phospholate-based CTX derivative (WPCTX) was prepared with facile synthetic procedure and satisfying yield. Several model guest molecules were selected to investigate WPCTX's host-guest properties. Based on the study of the host and model guest complexation, a tetraphenylethylene derivative from model guest was employed as a guest molecule (G) to form WPCTX⊃G nanoparticles (NPs) with WPCTX through further supramolecular self-assembly in water. Moreover, a hydrophobic fluorescent dye, Eosin Y(ESY) or Nile red (NiR), was encapsulated in WPCTX⊃G NPs to construct two types of artificial light-harvesting systems. Their high antenna effect demonstrated such NPs successfully mimicked light-harvesting systems in nature.

Multilevel Chirality Transfer from Amino Acid Derivatives to Circularly Polarized Luminescence-Active Nanoparticles in Aqueous Medium.

Chirality at different levels is widely observed in nature, but the clue to connect it all together, and the way chirality transfers among different levels are still obscure. Herein, a l-/d-lysine-based self-assembly system was constructed, in which two-step chirality transfer among three different levels was observed in aqueous solution. The chirality originated from the point chirality of amino acid derivatives l-/d-PyLys hydrochloride, and was transferred to the planar conformational chirality of water-soluble pillar[5]arene pR-/pS-WP5. Then, with the aid of pR-/pS-WP5, nanoparticles were formed that exhibited L-/R-handed circularly polarized luminescence with a dissymmetry factor of up to ±0.001, arising from pyrene chiral excimers. This multilevel chirality transfer not only provides a perspective to trace potential clues, and to pursue certain ways by which the chirality transfers, but also offers a strategy to create controllable CPL emission in aqueous media.

Selection of Planar Chiral Conformations between Pillar[5,6]arenes Induced by Amino Acid Derivatives in Aqueous Media.

Chiral α-amino acids play critical roles in the metabolic process in nearly all life forms. So far, chiral recognition of α-amino acids has mainly focused on the determination of l/d enantiomers. Herein, selection of planar chiral conformations between water-soluble pillar[5]arene WP5 and pillar[6]arene WP6 was observed due to α-side chain or ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides binding with WP5 and WP6, respectively. Therefore, α-side chain and ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides were recognized by observing the induced CD signal and its inversion. This is a rare example of being able to detect the chiral region around α-carbon of a chiral α-amino acid molecule.

Circularly polarized luminescent systems fabricated by Tröger's base derivatives through two different strategies.

The Tröger's base derivative rac-TBPP was synthesized and separated into two enantiomers R 2N -TBPP and S 2N -TBPP by chiral column chromatography. These compounds show a strong circularly polarized luminescence with g lum values of +0.0021, and -0.0025, respectively. The second way to fabricate the rac-TBPP-based CPL-active material is to co-gel the fluorescent rac-TBPP with a chiral ᴅ-glutamic acid gelator DGG by co-assembly strategy. At the molar ratio of rac-TBPP/DGG = 1:80, the g lum value of the co-gel was about three times higher than the g lum values of R 2N -TBPP and S 2N -TBPP enantiomers. Interestingly, the CPL handedness of the rac-TBPP/DGG co-gel could be adjusted effectively by changing their stoichiometric ratios.

Multiresponsive Supramolecular Theranostic Nanoplatform Based on Pillar[5]arene and Diphenylboronic Acid Derivatives for Integrated Glucose Sensing and Insulin Delivery.

A closed-loop "smart" insulin delivery system with the capability to mimic pancreatic cells will be highly desirable for diabetes treatment. This study reports a multiple stimuli-responsive insulin delivery platform based on an explicit supramolecular strategy. Self-assembled from a well-designed amphiphilic host-guest complex formed by pillar[5]arene and a diphenylboronic acid derivative and loaded with insulin and glucose oxidase, the obtained insulin-GOx-loaded supramolecular vesicles can selectively recognize glucose, accompanied by the structure disruption and efficient release of the entrapped insulin triggered by the high glucose concentration as well as the in situ generated H2 O2 and acid microenvironment during the GOx-promoted specific oxidation of glucose into gluconic acid. Moreover, such a "smart" supramolecular theranostic nanoplatform is able to function as both a glucose sensor and a controlled insulin delivery actuator. In vivo experiments further demonstrate that this smart supramolecular nanocarrier shows fast response to hyperglycemic circumstances and can effectively regulate the glucose levels in a mouse model of type I diabetes.

A Four-Armed Unsymmetrical Cryptand: From Two Different Host-Guest Interactions to Responsive Supramolecular Polymer.

By linking BMP32C10 and DB24C8 motifs together, a four-armed cryptand 1 is synthesized successfully, in which BMP32C10 motif can bind paraquat 2 while DB24C8 motif can complex dibenzylammonium salt 3 in spite of the electrostatic repulsion between guests 2 and 3. The base/acid-responsive supramolecular polymer is constructed further via two kinds of host-guest interactions between cryptand 1 and two homoditopic paraquat 4 and dibenzylammonium salt 5 similar to guests 2 and 3.

A Phosphine Oxide Functional Group Based [2]Rotaxane That Operates as a Multistable Molecular Shuttle.

A switchable [2]rotaxane based on a pyridinediamide crown ether macrocycle and a thread bearing phosphine oxide, urea, and dibenzylammonium functional groups was successfully developed and characterized by (1) H NMR and 2D NMR spectroscopy, mass spectrometry, and single-crystal analysis. The three recognition sites in the [2]rotaxane were sorted from strong to weak, according to their bonding abilities, so that the macrocycle could move along the thread from one side to the other in a directional way, operating as a multistable molecular shuttle.

Density Functional and Kinetic Monte Carlo Study of Cu-Catalyzed Cross-Dehydrogenative Coupling Reaction of Thiazoles with THF.

Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction of thiazoles with THF has been studied with the density functional theory method and kinetic Monte Carlo (kMC) simulations. Our results show that the previously proposed concerted metalation-deprotonation mechanism is unfavorable. On the basis of the DFT calculation and kMC simulation results, a new mechanism is proposed. In the favorable mechanism, the Cu(II) catalyst first combines with the thiazoles, forming an organocopper species that then binds to the THF radical. The rate-limiting step, C-C bond formation, is realized through an intramolecular structural rearrangement. The Cu catalyst works as a matchmaker to render the C-C bond formation. Kinetic Monte Carlo simulations demonstrate that one should be careful with the conclusions drawn simply from the calculated barriers.

Precise recognition of benzonitrile derivatives with supramolecular macrocycle of phosphorylated cavitand by co-crystallization method.

The importance of molecular docking in drug discovery lies in the precise recognition between potential drug compounds and their target receptors, which is generally based on the computational method. However, it will become quite interesting if the rigid cavity structure of supramolecular macrocycles can precisely recognize a series of guests with specific fragments by mimicking molecular docking through co-crystallization experiments. Herein, we report a phenylphosphine oxide-bridged aromatic supramolecular macrocycle, F[3]A1-[P(O)Ph]3, which precisely recognizes benzonitrile derivatives through non-covalent interactions to form key-lock complexes by co-crystallization method. A total of 15 various benzonitrile derivatives as guest molecules are specifically bound by F[3]A1-[P(O)Ph]3 in co-crystal structures, respectively. Notably, among them, crisaborole (anti-dermatitis) and alectinib (anti-cancer) with the benzonitrile fragment, which are two commercial drug molecules approved by the U.S. Food and Drug Administration (FDA), could also form a key-lock complex with F[3]A1-[P(O)Ph]3 in the crystal state, respectively.

Tröger's Base-Embedded Pillararenes─Macrocycles with Both Fixed and Conformational Chirality.

Tröger's base-embedded pillararenes (P[1]TB[3]A), which combine Tröger's base (TB) with dialkoxybenzene units, were prepared via a fragment-coupling macrocyclization strategy. The TB unit in macrocycle P[1]TB[3]A provides a fixed chiral source, while 1,4-alkoxybenzene segments flip quickly to change their arrangement, which could provide reversible conformational chirality for those macrocycles. This rare example of macrocycles holding both fixed and conformational chirality lays a good foundation for expanding pillararenes using the fixed chiral source.

Cu-catalyzed direct C-H bond functionalization: a regioselective protocol to 5-aryl thiazolo[3,2-b]-1,2,4-triazoles.

An efficient, regioselective C-5 arylation of thiazolo[3,2-b]-1,2,4-triazoles catalyzed by a simple copper catalyst was developed. This arylation proceeded smoothly and tolerated a variety of functional groups (44 examples). A wide range of functionalized thiazolo[3,2-b]-1,2,4-triazole derivatives were obtained in high yields (up to 99% yield). Possible catalytic cycles of the arylation were also discussed.

Synthesis of Tröger's base-based [3]arenes for efficient iodine adsorption.

Enantiomers of Tröger's base-based [3]arenes R6N-E[3] and S6N-E[3] were synthesized successfully as two optically pure Tröger's base-based macrocycles in which three Tröger's base subunits were incorporated. Among these Tröger's base-based[3]arenes, M[3] showed high absorption of iodine up to 4.02 g g-1 in vapor.

Host-guest system of a phosphorylated macrocycle assisting structure determination of oily molecules in single-crystal form.

X-ray crystallography is the most reliable method for structure elucidation and absolute configuration determination of organic molecules based on their single-crystal forms. However, many analytes are hard to crystallize because of their low melting points (an oily state at room temperature) or conformational flexibility. Here, we report the crystallization of a macrocycle, CTX[P(O)Ph] (host), which is a cyclotrixylohydroquinoylene (CTX) derivative, with 26 oily organic molecules (guests), which is applied for the structural determination of the guest with X-ray crystallography. With the aid of the host, CTX[P(O)Ph], the guest molecules were well-ordered with full occupancy in crystal structures. In most cases, at least one guest structure without any disorder could be observed; solvent masking was not necessary for the single crystal X-ray structural analysis, and thus the structures of the guests could be successfully determined, and the absolute configuration could be assigned reliably for chiral guests with this method. The crystallization mechanism was further discussed from theoretical and experimental perspectives, suggesting that the negative electrostatic potential surface of CTX[P(O)Ph] and noncovalent interactions between the host and guest were crucial for the ordered arrangements of the guest.

Planar Chirality for Acid/Base Responsive Macrocyclic Pillararenes Induced by Amino Acid Derivatives: Molecular Dynamics Simulations and Machine Learning.

Chirality is ubiquitous in nature, ranging from a DNA helix to a biological macromolecule, snail's shell, and even a galaxy. However, the precise control of chirality at the nanoscale is a challenge due to the structure complexity of supramolecular assemblies, the small energy differences between different enantiomers, and the difficulty in obtaining polymorphic crystals. The planar chirality of water-soluble pillar[5]arenes (called WP5-Na with Na ions in the side chain) host triggered by the addition of chiral L-amino acid hydrochloride (L-AA-OEt) guests and acid/base is rationalized by the relative stability of different chiral isomers, being estimated by molecular dynamics (MD) simulations and quantum chemical calculations. As an increase in the pH value, the change from a positive to a negative value of the free energy difference (ΔG) between two conformations, pR-WP5-Na⊃L-AA-OEt and pS-WP5-Na⊃L-AA-OEt, suggests an inversed preference of the pS-WP5-Na conformer induced by the deprotonated L-arginine ethyl ester (L-Arg-OEt) at pH = 14, which is supported by the circular dichroism (CD) experiments. On the basis of 2256 WP5-Na⊃L-Ala-OEt and 3299 WP5-Na⊃L-Arg-OEt conformers sampled from MD, the gradient boosting regression (GBR) model exhibits a satisfactory performance (R2 = 0.91) in predicting the chirality of WP5-Na complexations using host-guest binding descriptors, including the geometry matching and binding sites and modes (electrostatics and hydrogen bonding). The machine learning model also performs well on external tests of different hosts (using different side chains and cavity sizes) with the addition of 22 other different guests, with the average chirality prediction accuracy of ML versus experimental CD determinations of 92.8%. The easily accessible host-guest features, binding position coordination and size matching between the cavity and guest, exhibit a close correlation to the chirality of different macrocyclic molecules, water-soluble pillar[6]arenes (WP6) versus WP5, in complexation with different amino acid guests. The exploration of efficient host-guest features in ML displays the great potential of building a large space of various assembled systems and accelerating the on-demand design of chiral supramolecular systems at the nanoscale.

Cation controlled rotation in anionic pillar[5]arenes and its application for fluorescence switch.

Controlling molecular motion is one of hot topics in the field of chemistry. Molecular rotors have wide applications in building nanomachines and functional materials, due to their controllable rotations. Hence, the development of novel rotor systems, controlled by external stimuli, is desirable. Pillar[n]arenes, a class of macrocycles, have a unique planar chirality, in which two stable conformational isomers pR and pS would interconvert by oxygen-through-the-annulus rotations of their hydroquinone rings. We observe the differential kinetic traits of planar chirality transformation in sodium carboxylate pillar[5]arene (WP5-Na) and ammonium carboxylate pillar[5]arene (WP5-NH4), which inspire us to construct a promising rotary platform in anionic pillar[5]arenes (WP5) skeletons. Herein, we demonstrate the non-negligible effect of counter cations on rotational barriers of hydroquinone rings in WP5, which enables a cation grease/brake rotor system. Applications of this tunable rotor system as fluorescence switch and anti-counterfeiting ink are further explored.

Vertical distribution of dissimilatory iron reducing communities in the sediments of Taihu Lake.

The reduction of Fe(III) coupled with the oxidation of organic matter, primarily stimulated by dissimilatory iron-reducing bacteria (DIRB) under anoxic conditions, is a critical biogeochemical process in lacustrine sediments. Many single strains have been recovered and investigated, however, the changes in the diversity of culturable DIRB communities with sedimentary depth have not been fully revealed. In this study, 41 DIRB strains affiliated to ten genera of phylum Firmicutes, Actinobacteria, and Proteobacteria were isolated from the sediments of Taihu Lake at three depths (0-2 cm, 9-12 cm, and 40-42 cm), referring to distinct nutrient conditions. Fermentative metabolisms were identified in nine genera (except genus Stenotrophomonas). The DIRB community diversity and the microbial iron reduction (MIR) patterns vary in vertical profiles. The community abundance varied with the TOC contents in vertical profiles. The DIRB communities, containing 17 strains of 8 genera, were most diverse in the surface sediments (0-2 cm), where organic matter was most abundant among the three depths. 11 DIRB strains of five genera were identified in the 9-12 cm sediments with the lowest content of organic matter, while 13 strains of seven genera were identified in deep sediments (40-42 cm). Among the isolated strains, phylum Firmicutes dominated the DIRB communities at three depths, while its relative abundance increased with depth. Fe2+ ion was recognized as the dominant microbial ferrihydrite-reducing product of DIRB from 0 to 12 cm sediments. Instead, lepidocrocite and magnetite were the main MIR products of DIRB retrieved from 40 to 42 cm. The results indicate that the MIR driven by fermentative DIRB is crucial in lacustrine sediments and that the distribution of nutrients and iron (minerals) likely influences the diversity of DIRB communities in the lacustrine sediments.

New light on the ring-chain equilibrium of a hydrogen-bonded supramolecular polymer based on a photochromic dithienylethene unit and its energy-transfer properties as a storage material.

A novel, bifunctional, quadruple hydrogen-bonding ureido-pyrimidinone (UPy) unit bridged by photochromic dithienylethene (1) has been synthesized, which affords linear assemblies in solution and undergoes concentration-dependent ring-opening polymerization. The two UPy functional groups of 1 can dimerize intramolecularly to form a cyclic monomer with the two thienyl rings fixed in a parallel conformation, which prohibits its photocyclization. We exploited the photochemical reactivity and resonance difference of the linker of the bis-UPy derivative as well as using the more typical (1)H NMR, DOSY, and Ubbelohde viscometry methods to investigate for the first time the ring-chain polymerization mechanism. Moreover, we fabricated a mixed polymer film with a fluorescent dye noncovalently endcapping the linear photochromic assemblies through quadruple hydrogen bonds, which showed nondestructive fluorescent read-out ability for data storage by fluorescence resonance energy transfer (FRET) from the fluorescent dye to the closed form of the diarylethene.

Stoichiometry-Controlled Chirality Induced by Co-assembly of Tetraphenylethylene Derivative, γ-CD, and Water-Soluble Pillar[5]arene.

A stoichiometry-controlled chirality induction was successfully achieved through coassemblies of amphiphilic tetraphenylethylene derivative TPEA, γ-cyclodextrin (γ-CD), and water-soluble pillar[5]arene WP5 in aqueous solution. Stoichiometric variation of WP5 was found to be an effective strategy to induce topological transition between the pseudo[4]rotaxane and the vesicular form. Interestingly, the formation of pseudo[4]rotaxane triggered dual chirality induction from chiral γ-CD to TPEA (negative ICD1), and then, to dynamically racemic WP5 (positive ICD2), whereas both ICD1 and ICD2 were silent in the vesicular form.