2-O-Methylated ß-Cyclodextrin as an Effective Building Block to Construct Supramolecular Assemblies with Various Morphologies and Molecular Arrangements.

The preparation of supramolecular cyclodextrin (CD) assemblies and control of their assembly mode through guest inclusion in CD cavities have been actively studied. Contrarily, there are limited reports on the control of the assembly mode of guest-free CD molecules by external stimuli. Herein, we report the use of 2-O-methylated ß-cyclodextrin (2-Me-ß-CD) as an effective building block in fabricating supramolecular assemblies with diverse morphologies and molecular arrangements through assembly mode control by various stimuli, such as temperature and solvent. When methanol and diethyl carbonate were used as good and poor solvents, respectively, 2-Me-ß-CD formed an amorphous assembly through solvent evaporation on a polyethylene terephthalate (PET) substrate. Increasing the drying temperature and using crystalline substrates, such as highly oriented pyrolytic graphite (HOPG) and sapphire, changed the assembly mode of 2-Me-ß-CD to a head-to-tail channel assembly. However, when a 2-Me-ß-CD/1-propanol solution was mixed with linear alkanes as a poor solvent, 2-Me-ß-CD with head-to-head channel assembly was formed as a precipitate. Additionally, when the corresponding cyclic alkane was used as an alternative poor solvent, an organogel composed of 2-Me-ß-CD with head-to-head channel assemblies was obtained. The organogel obtained became a precipitate composed of 2-Me-ß-CD with cage-type assembly upon heating at 50 °C. Among the supramolecular assemblies fabricated in this study, the head-to-tail channel assembly is a rare molecular assembly of ß-CD and its derivatives. It possesses a modified columnar cavity that has potential applications in molecular recognition and sensing.

Highly Regulated Supramolecular Assembly of 2-O-Methylated α-Cyclodextrin to Construct Vertically Oriented Microrods on Graphite.

Precisely controlling self-assembled molecules to fabricate highly ordered nano/microstructures is a challenging task. Here, a simple precipitation technique with common solvents forms supramolecular microstructures with highly regulated molecular arrangements from a methylated derivative of α-cyclodextrin at the 2-O position (2-Me-α-CD). The formation of a head-to-tail channel assembly of 2-Me-α-CD through host-guest complexation with a solvent molecule such as benzene or cyclohexane yields well-defined hexagonal microrods. Specifically, the self-assembly of 2-Me-α-CD forms vertically aligned hexagonal microrods on a highly ordered pyrolytic graphite (HOPG) surface via epitaxial growth. This work should provide insight into the design of supramolecular building blocks for controlled self-assembly.

Visible Light-Induced Regio- and Enantiodifferentiating [2 + 2] Photocycloaddition of 1,4-Naphthoquinones Mediated by Oppositely Coordinating 1,3,2-Oxazaborolidine Chiral Lewis Acid.

A range of asymmetric photochemical transformations using visible light have recently become considerably attractive. Among the various approaches, chiral Lewis acid association to enones for [2 + 2] and ortho photocycloadditions and oxadi-π-methane rearrangements have shown to be very promising. Naturally, chiral Lewis acid coordination protects one of the prochiral faces of the C═C double bond, which enables an effective enantiodifferentiation in the following bond-forming process(es). Here, we studied regio- and enantiodifferentiating [2 + 2] photocycloaddition reactions of naphthoquinone derivatives mediated by chiral oxazaborolidines. A stereochemical control was quite challenging for the 2-ene-1,4-dione substrate, as a double coordination of Lewis acid essentially cancels out the face selectivity, and a mono-coordination to each carbonyl group leads to an opposite stereochemical outcome. Furthermore, a stepwise coordination in the ground state of Lewis acid in a 1:1 fashion was practically inaccessible. We found that the excited-state decomplexation is a key to accomplish high regio- and enantioselectivities in the photocycloaddition of an ene-dione.

Cyclodextrins with Multiple Pyrenyl Groups: An Approach to Organic Molecules Exhibiting Bright Excimer Circularly Polarized Luminescence.

We report a simple and effective approach to organic molecules exhibiting bright circularly polarized luminescence (CPL) by combining a chiral cyclic molecular scaffold and multiple excimer-enabling moieties. An α-cyclodextrin (CyD) scaffold was modified with six pyrenyl groups to obtain pyrene-cyclodextrins (PCDs) in a one-step synthesis from commercially available compounds. The PCDs exhibited high molar extinction coefficients (ϵ≈105  M-1  cm-1 ), polarized emission with a good dissymmetry factor (|glum |≈10-2 ), and quantum yield (Φf ≈0.5). Owing to the excellent photophysical properties of the PCDs, the circularly polarized luminescence brightness (BCPL ) reached 340 M-1  cm-1 . Photophysical and chiroptical studies of the PCDs with only five pyrene units and with linkers of various lengths connecting the CyD with the pyrene units revealed that the formation of a pyrene excimer in a spatially crowded environment is crucial for CPL anisotropy. This study paves the way for the development of bright CPL organic molecules.

Post-assembly Fabrication of a Functional Multicomponent Supramolecular Hydrogel Based on a Self-Sorting Double Network.

Living cells exhibit sophisticated functions because they contain numerous endogenous stimuli-responsive molecular systems that independently and cooperatively act in response to an external circumstance. On the other hand, artificial soft materials containing multiple stimuli-responsive molecular systems are still rare. Herein, we demonstrate a unique multicomponent hydrogel composed of a self-sorting double network prepared through a post-assembly fabrication (PAF) protocol. The PAF protocol allowed the construction of a well-ordered hydrogel with a dual-biomolecule response to two important biomolecules (adenosine triphosphate (ATP) and sarcosine). Such a hydrogel could not be prepared through a one-step mixing protocol. The resultant multicomponent hydrogel responded to ATP and sarcosine through gel-sol transition behavior programmed in an AND logic gate fashion. Finally, we applied the multicomponent hydrogel to the controlled release of an antibody.

Imaging-Based Study on Control Factors over Self-Sorting of Supramolecular Nanofibers Formed from Peptide- and Lipid-type Hydrogelators.

Multicomponent self-assembly is a fascinating strategy for the construction of smart soft materials. Among them, supramolecular hydrogels comprising self-sorting nanofibers have recently attracted significant attention owing to their rationally incorporated stimulus responsiveness. However, there have been limited investigations of the crucial factors that control the self-sorting phenomena. Here, we describe an imaging-based approach to evaluate the factors that control the formation of self-sorting nanofibers from peptide- and lipid-type hydrogelators. We screened a small library of hydrogelators with distinct chemical properties by direct visualization of their self-assembly behavior by using confocal laser scanning microscopy. Our systematic research identified two important factors that influence the self-sorting behavior of nanofibers: (i) the surface charge of the hydrogelators; and (ii) the hydrophobicity of the side chain on the peptide-type hydrogelators. We determined that the same net/surface charge on the hydrogelators and side chains with a lower hydrophobicity on the peptide-type hydrogelators were preferred. These findings, in combination with the previously reported kinetic factors, were used to design and successfully prepare a three-component orthogonal self-assembly composed of supramolecular nanofibers from peptide- and lipid-type hydrogelators and a cationic organorhodium complex. Our findings would be beneficial for the design of intelligent soft materials based on self-sorting phenomena.

Design Strategies of Stimuli-Responsive Supramolecular Hydrogels Relying on Structural Analyses and Cell-Mimicking Approaches.

Stimuli-responsive hydrogels are intriguing biomaterials useful for spatiotemporal controlled release of drugs, cells, and biological cues, cell engineering for various applications, and medical diagnosis. To date, many physical and chemical stimuli-responsive polymer hydrogels have been developed by chemical modification of polymer chains and cross-linking points. In particular, conjugation with biomolecules to polymers produced promising biomolecule-responsive hydrogels. These examples clearly indicate high potentials of stimuli-responsive hydrogels as promising biomaterials. In addition to polymer hydrogels, supramolecular hydrogels formed by the assembly of small molecules (hydrogelators) via noncovalent interactions have also been regarded as unique and promising soft materials due to their flexible programmability in rendering them stimuli-responsive with the larger macroscopic change (i.e., gel-sol transition). This Account describes our strategies for the rational design of stimuli-responsive supramolecular hydrogels and their biological applications. Following the detailed structural analysis of a lead hydrogelator that clearly indicates the appropriate sites for incorporation of stimuli-responsive modules, we designed supramolecular hydrogels capable of responding to simple physical (thermal and light) and chemical (pH and metal ions) stimuli. More importantly, biomolecule-responsive hydrogels were successfully developed by supramolecularly mimicking the complex yet well-ordered structures and functions of live cells containing multiple components (a cell-mimicking approach). Development of biomolecule-responsive supramolecular hydrogels has been difficult as the conventional strategy relies on the chemical incorporation of stimuli-responsive modules, owing to the lack of modules that can effectively respond to structurally diverse and complicated biomolecules. Inspired by natural systems where functional compartments (e.g., cell organelles) sophisticatedly interact with each other, we sought to integrate the two distinct microenvironments of supramolecular hydrogels (the aqueous cavity surrounded by fibers and the fluidic hydrophobic fiber domain) with other functional materials (e.g., enzymes, peptides or proteins, fluorescent chemosensors, or inorganic porous or layered nanomaterials) for biomolecule responses. In situ fluorescence microscopy imaging clearly demonstrated that chemical isolation and crosstalk are highly successful between the integrated microenvironments in supramolecular hydrogels, similar to organelles in living cells, which allow for the construction of unique optical response and sensing systems for biomolecules. Furthermore, programmed hybridization of our chemically reactive hydrogels with appropriate enzymes can provide an unprecedented universal platform for biomolecule-degradable supramolecular hydrogels. Such biomolecule-responsive hydrogels are a potentially promising tool for user-friendly early diagnostics and on-demand drug-releasing soft materials. We expect that our rational design strategies for stimuli-responsive supramolecular hydrogels by modification of chemical structures and hybridization with functional materials will inspire scientists in various fields and lead to development of novel soft materials for biological applications.

Chemically reactive supramolecular hydrogel coupled with a signal amplification system for enhanced analyte sensitivity.

Multicomponent supramolecular hydrogels are constructed for sensitive, naked-eye detection of small-molecule biomarkers. A dendritic self-immolative molecule and the corresponding enzyme as a signal amplification system were stably embedded in a hydrogen peroxide (H2O2)-responsive supramolecular hydrogel (BPmoc-F3), together with other enzymes. The nanostructure and mechanical strength of the hybrid BPmoc-F3 gel were not substantially diminished by incorporation of these multiple components in the absence of target biomarkers, but could be destroyed by addition of the biomarker through the multiple enzymatic and chemical cascade reactions operating in combination within the gel matrix. The sensitivity to biomarkers such as H2O2, glucose, and uric acid, detected by gel-sol transition, was significantly enhanced by the signal amplification system. An array chip consisting of these multicomponent hydrogels enabled the detection of the level of hyperuricemia disease in human plasma samples.

Supramolecular nanosheet formation-induced photosensitisation mechanism change of Rose Bengal dye in aqueous media.

Development of two-dimensional materials and exploration of their functionalities are significant challenges due to their potential. In this study, we successfully fabricated a supramolecular nanosheet composed of amphiphilic Rose Bengal dyes in an aqueous medium. Furthermore, we elucidated a distinct change in the photosensitisation mechanism induced by nanosheet formation.

Crystalline supramolecular nanofibers based on dehydrobenzoannulene derivatives.

Supramolecular nanofibers (SNFs) composed of low-molecular-weight π-conjugated molecules exhibit attractive optical and electrical properties and are expected to be the next optoelectronic materials. In this work, five crystalline SNFs have been constructed from three dehydrobenzoannulene (DBA) derivatives. The DBAs were designed to assemble in one dimension in a strategy based on anisotropic crystal growth. The crystallinity of the SNFs allowed the molecular arrangements in the SNFs to be determined. Therefore the mechanism of construction and correlations between the molecular arrangements and optical and electrical properties could be considered. The results clearly indicate that the properties of the SNFs are affected by the chemical structures and molecular arrangements. Moreover, one of the SNFs exhibits a high charge-carrier mobility (Σµ=0.61 cm(2) V(-1) s(-1)) because of its crystallinity and appropriate molecular arrangement. This systematic experimental study based on a proposed strategy has provided information for improving the electrical properties of SNFs. This strategy will lead to highly functional SNFs.

Preparation and temperature-controlled morphology of helical microrods composed of supramolecular α-cyclodextrin assemblies.

Significant efforts have been devoted so far to artificially fabricate supramolecular helical nano- and microstructures through the regulated assembly of biological and synthetic building blocks. However, the preparation of supramolecular helical structures with a regulated morphology remains challenging. Here, helical microrods composed of supramolecular α-cyclodextrin (α-CD) assemblies were fabricated by allowing an α-CD/1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)/2-pentanol mixture to stand at 30-60 °C under high humidity conditions. The morphology could be controlled by temperature to produce helical microrods with a regulated pitch and length. These helical rods can be applied as optical devices, chiral separation devices and asymmetric catalysts.

Radioluminescence from polymer dots based on thermally activated delayed fluorescence.

We demonstrate that polymer dots doped with thermally activated delayed fluorescence (TADF) molecules clearly exhibit blue radio-luminescence upon hard X-ray and electron beam irradiation, which is a new design for nano-sized scintillators.

Interactions between dehydrobenzo[12]annulene (DBA) and gas molecules: do the preorganized acetylenes work cooperatively?

Intermolecular interactions of the cyclic conjugated molecule (DBA) with hydrogen, nitrogen and carbon dioxide molecules were evaluated by high level ab initio calculations.

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly.

Photosensitizers (PSs) are critical substances with considerable potential for use in non-invasive photomedicine. Type I PSs, which generate reactive radical species by electron transfer from the excited state induced via photoirradiation, attracted much attention because of their suitability for photodynamic therapy (PDT) irrespective of the oxygen concentration. However, most organic PSs are type II, which activates only oxygen, generating singlet oxygen (1O2) via energy transfer from the triplet state. Here, we proposed a strategy to form type I supramolecular PSs (SPSs) utilizing the charge-separated state induced by self-assembly. This was demonstrated using a supramolecular assembly of fluorescein, which is a type II PS in the monomeric state; however, it changes to a type I SPS via self-assembly. The switching mechanism from type II to I via self-assembly was clarified using photophysical and electrochemical analyses, with the type I SPS exhibiting significant PDT effects on cancer cells. This study provides a promising approach for the development of type I PSs based on supramolecular assemblies.

Porphyrin covalent organic nanodisks synthesized using acid-assisted exfoliation for improved bactericidal efficacy.

Porphyrin covalent organic nanodisks (CONs) were synthesized by exfoliating covalent organic frameworks (COFs) in acidic aqueous solutions at pH 4. The synthesized CONs showed remarkable bactericidal activity against Escherichia coli owing to enhanced generation of singlet oxygen upon visible light irradiation.

Construction of 1D π-stacked superstructures with inclusion channels through symmetry-decreasing crystallization of discotic molecules of C3 symmetry.

Supramolecular architectures that possess both 1D π-stacked columns and inclusion channels were constructed by symmetry-decreasing crystallization of dehydrobenzo[12]annulene (DBA) derivatives with naphthyl arms and C(3) symmetry. The crystallization can be interpreted as i) formation of a two-fold column, ii) layer formation, and iii) lamination of the layer accompanied by guest inclusion.

Terminal Trialkylsilyl Substituent Effect of Janus-type Molecular Tubes on the Inclusion of Unsaturated Fatty Acid Esters.

A new Janus-type cyclodextrin (CD) molecular tube bearing seven triisopropylsilyl (TIPS) groups at one end is synthesized from a heptakis(6-O-triisopropylsilyl)-ß-cyclodextrin (TIPS-ß-CD) dimer possessing multiple linkers through the selective removal of seven TIPS groups at the other end. This Janus-type CD tube exhibits a selective inclusion ability for a cis-fatty acid ester over the corresponding trans-fatty acid ester. In addition, the CD tube shows a twofold higher inclusion ability for unsaturated fatty acid esters than the corresponding CD tube bearing seven tert-butyldimethylsilyl (TBDMS) groups, indicating that the molecular size of the terminal substituents remarkably affects the inclusion ability of the CD tube.

A cyanine dye based supramolecular photosensitizer enabling visible-light-driven organic reaction in water.

We report the aggregation-induced photosensitizing activity of a cyanine dye in water and the mechanism. In addition, using the supramolecular assembly, visible-light-driven photooxidation of hydrophobic aromatic compounds in water was successfully performed.

Supramolecular organogel formation through three-dimensional α-cyclodextrin nanostructures: solvent chirality-selective organogel formation.

Novel supramolecular organogels were efficiently formed by mixing a 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solution of α-cyclodextrin (α-CD) with 1- or 2-butanol via the formation of three-dimensional hexagonal nanostructures composed of head-to-tail α-CD channel assemblies. Mixing (R)- and (S)-2-butanol with an α-CD/HFIP solution realized (S)-2-butanol-selective organogel formation.

Control of Guest Inclusion and Chiral Recognition Ability of 6-O-Modified ß-Cyclodextrins in Organic Solvents by Aromatic Substituents at the 2-O Position.

The host-guest chemistry and applications of cyclodextrins in aqueous media is well established. However, a comprehensive study in organic solvents is lacking. Here, we report the design and synthesis of 6-O-tert-butyldimethylsilylated ß-cyclodextrin (TBDMS-ß-CD) bearing various aromatic substitutions at the 2-O position and their inclusion complex formation with aromatic guests in nonpolar organic solvents. Compared to the parent TBDMS-ß-CD, these derivatives exhibit at least a 10-fold increase in inclusion ability toward pyrene through cooperative guest binding with the CD cavity and the aromatic substituents at the 2-O position. The type of the aromatic substituent largely affects the chiral recognition ability of TBDMS-ß-CD toward 1-(1-naphthyl)ethylamine in cyclohexane. A TBDMS-ß-CD derivative with a p-tolyl substituent has a remarkable chiral selectivity for the (S)-1-(1-naphthyl)ethylamine over the corresponding (R)-isomer (KS /KR =4.1±0.5), whereas a TBDMS-ß-CD derivative with a 2-picolyl substituent shows the inverse chiral selectivity (KR /KS =8.7±0.6).