Supramolecular flow chemistry: Construction of multiscale supramolecular assemblies by micro/nanofluidic techniques

The rapid and precise fabrication of multiscale supramolecular assemblies using micro/nanofluidic techniques has emerged as a dynamic area of research in supramolecular chemistry, materials chemistry, and organic chemistry. This review summarizes the application of micro/nanofluidic techniques in constructing supramolecular assemblies, including nanoscale supramolecular assemblies such as macrocycles and cages, microscale supramolecular assemblies such as metal organic frameworks (MOFs) and covalent organic frameworks (COFs), and macroscale supramolecular assemblies such as supramolecular hydrogels. Compared to conventional synthesis methods, micro/nanofluidic techniques for the production of supramolecular assemblies have significant advantages, including enhanced safety, high reaction rates, improved selectivity/yield, and scalability. Additionally, micro/nanofluidic systems facilitate the creation of precisely controllable micro/nanoconfined environments, allowing for a unique flow behavior that improves our understanding of the supramolecular self-assembly process. Such systems may also lead to the development of novel supramolecular assemblies that differ from those generated via traditional methods.

Label-free Fluorescent Sensor for Probing Heparin-Protein Interaction Based on Supramolecular Assemblies

In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported.Heparin,the bioactive polyanions,formed supramolecular assemblies with cationic surfactant cetyltrimethyl ammonium bromide (CTAB).The environment-dependent dye pyrene,encapsulated in hydrophobic interiors of the supramolecular assemblies worked as the fluorescence probe.Once the heparin-binding protein was added,competing interactions of protein with heparin would weaken the interaction between CTAB and heparin.As a result,the noncovalently sequestered pyrene would be released upon disassembly and the fluorescence of the released pyrene was subsequently decreased.The binding events were exemplified by protamine and Tat peptide,these processes were also verified by DLS and TEM.Such a strategy is appealing as organic synthesis was traded off against supramolecular assembly.This label-free fluorescent system is simple,selective,convenient,and can serve as a good complement to other existing methods,also this method has the potential for preprimary drug screening.

CO_(2) and photo-controlled reversible conversion of supramolecular assemblies based on water soluble pillar[5]arene and coumarin-containing guest

In this communication,a new supramolecualr amphiphile was successfully constructed based on water soluble pillar[5]arene and a unique guest which contain a CO_(2) responsive tertiary amine unit and a UV responsive coumarin group.When guest molecule 1 dispersed in water,it self-assembled into sheet-like structures.Upon bubbling CO_(2),1 transformed into 1 H due to the tertiary amine unit was protonated,accompany the nano-sheets transformed into vesicles.Further irradiation of 1 H with 365 nm light for 3 h,the coumarin group reacted with each other to form bola-type amphiphie 2 H.In this case,vesicles collapsed and re-assembled into nano-tubes.However,when addition of WPS into the solution of 1 H,the vesicles transformed into micelles,this is due to the formation of supramolecular amphiphile WP5&1 H.Upon irradiation of WP5&1 H with 365 nm light for 3 h,nano-ribbons observed instead of micelles in the solution.Notably,nanotubes from 2 H could also transform into nano-ribbons after adding WPS.The selfassembly process and the resultant assemblies were characterized by TEM,SEM,DLS,SAXS and NMR technologies.Due to both CO_(2) and light are "green" for living organisms,we anticipated our system can offer the possibilities in "on demand" drug absorption and release.

Controllable macrocyclic supramolecular assemblies in aqueous solution

A series of macrocycles, including crown ethers, cyclodextrins, calixarenes, pillararenes and cucurbiturils, are well known to be able to associate various organic/inorganic/biological guest molecules and ions in their well-defined cyclic cavities to form stable host-guest complexes and supramolecular systems through the cooperative contributions of various non-covalent interactions.When one or more functional groups are attached to the cavity of macrocycles or guest molecules, enhanced and/or controlled host-guest associations may take place, leading to not only improved host-guest binding abilities but also fascinating properties.In this review, some representative contributions in the construction of controllable macrocyclic supramolecular assemblies in aqueous solution are presented with an emphasis on the stimuli-responsive control manner and wide applications of this property.

Nature-inspired supramolecular assemblies for precise biomedical imaging and therapy

To the editor:The precise diagnosis and effective therapy of refractory diseases,such as neurodegenerative diseases,coronary heart diseases and cancers,is critical to increase the survival rate and improve the life quality of patients.Most of the conventional small molecular medicines are heavily associated with the limitations of poor solubility,low targeting efficiency,inducing drug resistance and systemic toxicity,promoting scientists to develop new strategies for overcoming these limitations.

One-, Two-, and Three-Dimensional Supramolecular Assemblies Based on Tubular and Regular Polygonal Structures of Pillar[n]arenes

Pillar[n]arenes,which were first reported by our groupin2008,arepromisingmacrocycliccompounds in supramolecular chemistry.The simple,tubular,and highly symmetrical shape of pillar[n]arenes has allowed various supramolecular assemblies with well-defined structures to be constructed.

Exploring the Transferability of Large Supramolecular Assemblies to the Vacuum-Solid Interface

We present an interplay of high-resolution scanning tunneling microscopy imaging and the corresponding theoretical calculations based on elastic scattering quantum chemistry techniques of the adsorption of a gold-functionalized rosette assembly and its building blocks on a Au(111)surface with the goal of exploring how to fabricate functional 3-D molecular nanostructures on surfaces.The supramolecular rosette assembly stabilized by multiple hydrogen bonds has been sublimed onto the Au(111)surface under ultra-high vacuum conditions;the resulting surface nanostructures are distinctly different from those formed by the individual molecular building blocks of the rosette assembly,suggesting that the assembly itself can be transferred intact to the surface by in situ thermal sublimation.This unanticipated result will open up new perspectives for growth of complex 3-D supramolecular nanostructures at the vacuum-solid interface.

Supramolecular Assemblies of Three New Metronidazole Derivatives Constructed with Various Dihydroxy-benzoic Acids via Hydrogen Bonds

Metronidazole(MTZ)is an important antibiotic,which has been widely applied to cure protozoal and bacterial diseases for human beings or animals.Herein,three novel drug supramolecular crystals constructed by MTZ with 2.5-dihydroxy-benzoic acid(2.5-DHBA)(1),2.6-dihydroxy-benzoic acid(2.6-DHBA)(2)and 3,5-dihydroxy-benzoic acid(3.5-DHBA)(3),respectively,have been discovered.The hydrogen bonds of N-H…O(O-H…N).C-H…O and O-H…O play important roles in the 3D supramolecular framework formation for crystals 1-3.Interestingly.due to the vary locations of the substituent groups,the two-dimensional layers in crystals 1 or 2 are constructed via intermolecular hydrogen bonds between MTZ and 2,5-DHBA or 2.6-DHBA,while in crystal 3 water molecules play a significant role except the intermolecular hydrogen bonds between MTZ and 3,5-DHBA.In addition,five synthons of I R^22(8),ⅡR3(9)in crystal 1,ⅢR1(4),ⅣR2(8)in crystal 2 andⅤR2(7)in crystal 3 formed through various hydrogen bonds are founded in this work.Systematic studies of syntheses,crystal structures and thermal analysis are reported.

Facile synthesis of azobenzene-embedded conjugated macrocycles for optically switchable single-crystal transistors and tunable supramolecular assemblies

A series of newπ-conjugated macrocycles(AzoM-n-E,n 1–3)incorporating=azobenzene units have been synthesized by a facile strategy in one-pot reaction.The resultant azobenzene-embedded macrocycles feature intrinsic photoresponsive behaviors and intriguing supramolecular assembling properties.The smallest macro-cycle AzoM-1-E with a rigid planar conjugated backbone structure is used to prepare the single crystal transistors,showing reversible optical tunability.The moderate size macrocycle AzoM-2-E assembles into a dimer in the form of interpenetration throughπ-πstacking between azobenzene units.The largest macrocycle AzoM-3-E with enhancedflexibility can adaptively assemble with various types of electron-deficient guests accompanied by distortion of azobenzene.Typically,AzoM-3-E assembles with the planar F4-TCNQ to form a tetragonal geometry by C-F⋅⋅⋅π and π-π interactions,while the assembly with ellipsoidal C70 viaπ-πinteractions induces AzoM-3-E to form a boat-shaped geometry.This work will shed new light on the development of functional conjugated macrocycles in organic electronics.

Supramolecular assemblies of cucurbit[n]urils and 4-aminopyridine controlled by cucurbit[n]uril size(n=5,6,7 and 8)

The binding interactions between 4-aminopyridine(4-AP) and a series of cucurbit[n]urils(Q[5], Q[6],TMe Q[6], Q[7], Q[8]) have been studied using1H NMR spectroscopy, UV–vis absorption spectroscopy,isothermal titration calorimetry(ITC) and X-ray crystallography. The data indicates that the Q[5]@4-AP complex exhibits exo binding, which is not observed in the other four host-guest complexes. Furthermore,X-ray crystallography clearly reveals how the Q[n]s bind with 4-AP to form complexes, for example Q[5]forms an outer-surface complex, whilst Q[6], TMe Q[6] and Q[7] formed 1:1 host and guest type complexes, and Q[8] formed a stable 1:2 ternary complex due to its large cavity, which can accommodate two 4-AP molecules.

Hydrothermal Synthesis and Crystal Structure of a New Supramolecular Channel Framework Based on Cu Complexes and Polyoxovanadate:[Cu(I)(phen)_2]_5[HV_(15)O_(36)(Cl)]_(0.65)[H_3V_(16)O_(38)(Cl)]_(0.35)·2H_2O

A new compound [Cu（I）（phen）2]5[HV15O36（Cl）]0.65[H3V16O38（Cl）]0.35·2H2O 1 （phen = 1,10′-phenanthroline） has been prepared from the hydrothermal reaction of V2O5, CuCl, phen, H2C2O4·2H2O, THMAM （tris（hydroxymethyl）aminomethane） and H2O in the molar ratio of 3：1：1：0.5：2.5：1400. Compound 1 crystallizes in the space group P42212 of the tetragonal system with a = b = 21.5009（8）, c = 28.401（2） A, V= 13129.5（12） A^3 Z = 4, Dc = 1.800 g/cm^3, μ（MoKa） = 1.932 mm^-1, λ（MoKa） = 0.71073 A, F（000） = 7063.4, C120H81.20ClCu5N20O38.7V15.35, Mr = 3557.58, the final R = 0.0594 and wR= 0.1320 for 7761 observed reflections （I 〉 2σ（I））. Structure analysis shows that 1 exhibits a 3D channel framework formed by the supramolecular assembly of Cu complexes and polyoxovanadate clusters via intermolecular hydrogen bonding, and the channels contain Cu complexes. Other characterizations by elemental analysis, XPS, IR, XRD and thermal analysis are also described.

Formation of Amino Acid Bridged Zinc Bisporphyrinethylenediamine Linear Supramolecular Array: UV-visible and ~1HNMR evidence

Coordination behavior of bidentate ligand ethylenediamine with a new chiral zine bisporphyrin O.O-C,-AA-C,-(TPP),Zn, was investigated by Uv-Vis titration and 'H-NMRspectroscopy. which further evidenced that ac-c,-AA-c,-(TPP)Zn, tends to form linear assemblywith ethylenediamine in chloroform.

Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging

Phototherapeutic nanoplatforms that combine photodynamic therapy(PDT)and photothermal therapy(PTT)with the guidance of photoacoustic(PA)imaging are an effective strategy for the treatment of tumors,but establishing a universal method for this strategy has been challenging.In this study,we present a supramolecular assem-bly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent(PcDA)via the anion and cation supramolec-ular interaction between two water-soluble phthalocyanine ramifications,PcD and PcA.This approach promotes the absorption of energy,thus enhancing the genera-tion of reactive oxygen species(ROS)and heat by PcDA,improving its therapeutic efficacy,and overcoming the low photon utilization efficiency of conventional PSs.Notably,after the intravenous injection of PcDA,neoplastic sites could be clearly visualized using PA imaging,with a PA signal-to-liver ratio as high as 11.9.Due to these unique features,PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation.This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.

Phenazine-based supramolecular photosensitizing assemblies:A“smart”selectivity control on catalytic activity of Pd(Ⅱ)nanoparticles

Photosensitizing supramolecular assemblies based on a phenazine derivative(PPA)have been developed,which show a strong affinity toward Pd2+ions to generate supramolecular ensemble PPA@Pd nanoparticles(NPs).The PPA@Pd NPs catalyse the Suzuki cross-coupled reaction under mild conditions(aerial conditions,mixed aqueous media,and visible light radiations).Although PPA@Pd NPs exhibit a strong affinity for arylboronic acid and could catalyse homocoupling of arylboronic acid,the preference of PPA assemblies for aryl halide directed the course of reactions toward the formation of cross-coupled products.The electron-rich PPA assemblies not only facilitate the oxidative addition step through photoinduced electron transfer to Pd^(2+)ions but also bring the reactants closer to the catalytic sites by selective interactions with aryl halides in the presence of arylboronic acid under visible light irradiation.The efficiency of PPA@Pd NPs to catalyse the Suzuki crosscoupled reaction has been demonstrated for the synthesis of unsymmetrically substituted terphenyl derivatives.

Recent advances in post-chiroptical manipulation of supramolecular aggregates assembled with molecular modules

Recently,various supramolecular assembly systems have been identified where the pre-existing chiral supramolecular structure can be manipulated through environmental adjustments,such as temperature,solvent,and concentration.These changes result in diverse microscopic morphologies during the assembly process and induce chiroptical variations,particularly in circular dichroism(CD)and circularly polarized luminescence(CPL)spectra.These chiroptical properties serve as direct indicators of the chiral supramolecular structure and hold promise for applications in sensing,molecular recognition,asymmetric synthesis,and material science.This review focuses on research published in the last five years,highlighting instances where assembled structures aggregated by small organic molecular modules demonstrate in-situ chiroptical changes through external condition control.It categorizes and discusses different modes of regulation,aiming to offer insights and guidelines for exploring dynamic changes in assembly processes and designing in-situ adjustable structures of assembly modules.

In situ thermoresponsive supramolecular assembly for switchable circularly polarized luminescence

The dynamic regulation of circularly polarized luminescence(CPL)holds profound significance in various fields,such as highlevel information storage and encryption.Here we developed a chiral amphiphilic molecule,CPSB-GLU-PEG350(CGP),composed of aggregation-induced emission(AIE)chromophores(Z)-4-(1-cyano-2-phenylvinyl)benzoic acid(CPSB),a chiral linker Glutamic acid and polyethylene glycol(PEG)thermoresponsive segments.Within the self-assembled supramolecular system formed by CGP,we have achieved in-situ temperature-responsive chiral structures,facilitating the thermal control switch of the CPL signal.Molecular dynamics simulations demonstrate the distinct behaviors of AIE and PEG units during the temperature-variable assembly process.Furthermore,by co-assembling achiral dye molecules with CGP,we have expanded the color range of the temperature-responsive CPL assembly system in situ and confirmed the occurrence of circularly polarizedF?rster resonance energy transfer(C-FRET)phenomenon in this process,which successfully enriched the strategies for in-situ CPL control in aqueous phases.In addition,the contactless radiative energy transfer of CPL can also be realized in this system,exhibiting more flexible temperature regulation of the CPL signal.This study provides a convenient and universal strategy for the construction of dynamically smart chiroptical materials.

Synergistic fluorescent hydrogel actuators with selective spatial shape/color-changing behaviors via interfacial supramolecular assembly

Biomimetic intelligent polymeric hydrogel actuators with cooperative fluorescence-color switchable behaviors are expected to find great potential applications in soft robotics,visual detection/display,and camouflage applications.However,it remains challenging to realize the spatial manipulation of synergistic shape/color-changing behaviors.Herein,we report an interfacial supramolecular assembly(ISA)approach that enables the construction of robust fluorescent polymeric hydrogel actuators with spatially anisotropic structures.On the basis of this ISA approach,diverse 2D/3D soft fluorescent hydrogel actuators,including chameleon-and octopi-shaped ones with spatially anisotropic structures,were facilely assembled from two different fluorescent hydrogel building blocks sharing the same physically cross-linked agar network.Spatially control over synergistic shape/color-changing behaviors was then realized in one single anisotropic hydrogel actuator.The proposed ISA approach is universal and expected to open promising avenues for developing powerful bioinspired intelligent soft actuators/robotics with selective spatial shape/color-changing behaviors.

Regulating photothermal properties of near-infrared croconaine dyes by supramolecular assembly

The photochemical and photophysical properties of near-infrared(NIR)dyes are significantly influenced by their aggregation state and mesoscopic morphology.However,beyond chemical synthesis,the regulation mechanisms for the properties of NIR dyes,particularly with respect to photothermal properties of the aggregates,are not yet fully understood.Here,we investigate the photothermal behaviors of croconaine-based(CroA)NIR dyes containing dipeptide or amino acids moieties.The introduction of hydrogen bonding promotesπ-πstacking of croconaine center,which can efficiently regulate aggregation states and assembly structures in isopropanol.Under laser irradiation,CroA aggregates undergo aggregation-dissociation transition,the in-situ monomer generation process regulates two parameters of photothermal performance:heating rates and plateau photothermal temperatures.This study reveals the regulation effect of non-covalent bonding interactions on CroA aggregates,highlighting supramolecular assembly strategy not only facilitates to construct of photothermal nanomaterials with well-defined structures,but also provides an alternative and effective method for regulating photothermal performance of NIR dyes.

Pyrrole/macrocycle/MOF supramolecular co-assembly for flexible solid state supercapacitors

Supramolecular assemblies constructed through the encapsulation of conductive polymers(CPs)by macrocyclic molecules have attracted increasing interest in the fields of supramolecular chemistry and electrochemistry.In this work,an effective strategy was reported to improve the stability and conductivity of CPs by electrochemically constructing different supramolecular assemblies composed of macrocycles and CPs.Typically,we uploaded zinc-based MOF(ZIF-8)onto carbon nanotube film(CNTF)and further electrically deposited macrocycles and CPs to gain the flexible conductive electrodes.Herein,five different supramolecular macrocycles,includingα-cyclodextrin(α-CD),sulfato-β-cyclodextrin(SCD),sulfonatocalix[4]arene(SC[4]),cucurbit[6]uril(CB[6])and cucurbit[7]uril(CB[7])were utilized and the electrochemical performances of the assembly electrodes increased in an order ofα-CD<SCD<SC[4]<CB[6]<CB[7],significantly improving the areal capacitance up to 1533 mF/cm^(2).This strategy may provide a new way for the application of macrocyclic supramolecules in electrochemical systems.

Multicolor Luminescent Carbon Nanoparticles： Synthesis, Supramolecular Assembly with Porphyrin, Intrinsic Peroxidase-Like Catalytic Activity and Applications

Luminescent carbon nanoparticles （CNPs） are newcomers to the world of nanomaterials and have shown great impact in health and environmental applications as well as being promising building blocks for future nanodevices because of their fascinating photoluminescence and potential to serve as nontoxic replacements for traditional heavy-metals-based quantum dots. Herein, fluorescent CNPs have been prepared from candle soot by re fluxing with HNO3 and subsequently separated by a single centrifugation. The CNPs can be represented by the empirical formula C1Ho.677Oo.586No.o15Nao.069, and have a size of 20-100 nm, height of 3.0 nm, lifetime of 7.31 ns ＋ 0.06 ns and quantum yield of -1.7%. Further studies demonstrate that： （1）the as-prepared CNPs exhibit excellent stability in biological media and their luminescence intensity does not change with ionic strength or pH in the physiological and pathological range of pH 4.5-8.8; （2） CNPs can act as electron donors and transporters and porphyrin can assemble onto CNPs through electrostatic and ^-stacking interactions to form porphyrin-CNPs supramolecular composites; （3）CNPs have strong intrinsic peroxidase-like activity. Based on this intrinsic peroxidase activity, a simple, cheap, and highly selective and sensitive colorimetric and quantitative assay has been developed for the detection of glucose levels. This assay has been used to analyze real samples, such as diluted blood and fruit juice.