Noncovalent Modulation of Chemoselectivity in the Gas Phase Leads to a Switchover in Reaction Type from Heterolytic to Homolytic to Electrocyclic Cleavage.

In the gas phase, thermal activation of supramolecular assemblies such as host-guest complexes leads commonly to noncovalent dissociation into the individual components. Chemical reactions, for example of encapsulated guest molecules, are only found in exceptional cases. As observed by mass spectrometry, when 1-amino-methyl-2,3-diazabicyclo[2.2.2]oct-2-ene (DBOA) is complexed by the macrocycle ß-cyclodextrin, its protonated complex undergoes collision-induced dissociation into its components, the conventional reaction pathway. Inside the macrocyclic cavity of cucurbit[7]uril (CB7), a competitive chemical reaction of monoprotonated DBOA takes place upon thermal activation, namely a stepwise homolytic covalent bond cleavage with the elimination of N2 , while the doubly protonated CB7⋅DBOA complex undergoes an inner-phase elimination of ethylene, a concerted, electrocyclic ring-opening reaction. These chemical reaction pathways stand in contrast to the gas-phase chemistry of uncomplexed monoprotonated DBOA, for which an elimination of NH3 predominates upon collision-induced activation, as a heterolytic bond cleavage reaction. The combined results, which can be rationalized in terms of organic-chemical reaction mechanisms and density-function theoretical calculations, demonstrate that chemical reactions in the gas phase can be steered chemoselectively through noncovalent interactions.

Rapid Estimation of Binding Constants for Cucurbit[8]uril Ternary Complexes Using Electrochemistry.

Supramolecular complexes are of fundamental interests in biomedicines and adaptive materials, and thus facile methods to determine their binding affinity show usefulness in the design of novel drugs and materials. Herein, we report a novel approach to estimate the binding constants KG2 of cucurbit[8]uril-methyl viologen-based ternary complexes (CB8-MV2+-G2) using electrochemistry, achieving high precision (±0.03) and practical accuracy (±0.32) in logKG2 and short measurement time (<10 min). In particular, we have uncovered a linear correlation (R2 > 0.8) between the reduction potential of CB8-MV2+-G2 ternary complexes and their reported binding constants from isothermal titration calorimetry, which allow a calibration curve to be plotted based on 25 sample complexes. Mechanistic investigation using experimental and computational approaches reveals that this correlation stems from the dynamic host-guest exchange events occurring after the electron transfer step. Binding constants of unknown ternary complexes, where G2 = hydrocarbons, were estimated, illustrating potential applications for sparsely soluble second guests.

Ultrahigh binding affinity of a hydrocarbon guest inside cucurbit[7]uril enhanced by strong host-guest charge matching.

Cucurbit[7]uril (CB[7]) is an artificial macrocyclic molecule that can form exceptionally strong host-guest complexes with binding constants higher than that of the biotin-avidin complex. Despite notable experimental efforts, there do not exist large-scale computational investigations on finding strongly binding guests of CB[7]. Herein, we develop a computational approach based on large-scale molecular modelling to predict strongly binding hydrocarbon motifs. Our results indicate that an expanded cubane (PubChem ID 101402794) will be the most strongly binding hydrocarbon guest of CB[7] among the hundreds of thousands of hydrocarbons in the PubChem database, achieving a binding affinity significantly stronger than those reported in preceding experimental studies. Our findings highlight the important role of charge complementarity in the form of quadrupole electrostatic interactions in enabling the ultrahigh binding affinity of nonpolar guest molecules with CB[7], in addition to other known contributions such as van der Waals interactions and high-energy water release.

Active Nanorheology with Plasmonics.

Nanoplasmonic systems are valued for their strong optical response and their small size. Most plasmonic sensors and systems to date have been rigid and passive. However, rendering these structures dynamic opens new possibilities for applications. Here we demonstrate that dynamic plasmonic nanoparticles can be used as mechanical sensors to selectively probe the rheological properties of a fluid in situ at the nanoscale and in microscopic volumes. We fabricate chiral magneto-plasmonic nanocolloids that can be actuated by an external magnetic field, which in turn allows for the direct and fast modulation of their distinct optical response. The method is robust and allows nanorheological measurements with a mechanical sensitivity of ∼0.1 cP, even in strongly absorbing fluids with an optical density of up to OD ∼ 3 (∼0.1% light transmittance) and in the presence of scatterers (e.g., 50% v/v red blood cells).

Self-propelling nanomotors in the presence of strong Brownian forces.

Motility in living systems is due to an array of complex molecular nanomotors that are essential for the function and survival of cells. These protein nanomotors operate not only despite of but also because of stochastic forces. Artificial means of realizing motility rely on local concentration or temperature gradients that are established across a particle, resulting in slip velocities at the particle surface and thus motion of the particle relative to the fluid. However, it remains unclear if these artificial motors can function at the smallest of scales, where Brownian motion dominates and no actively propelled living organisms can be found. Recently, the first reports have appeared suggesting that the swimming mechanisms of artificial structures may also apply to enzymes that are catalytically active. Here we report a scheme to realize artificial Janus nanoparticles (JNPs) with an overall size that is comparable to that of some enzymes ∼30 nm. Our JNPs can catalyze the decomposition of hydrogen peroxide to water and oxygen and thus actively move by self-electrophoresis. Geometric anisotropy of the Pt-Au Janus nanoparticles permits the simultaneous observation of their translational and rotational motion by dynamic light scattering. While their dynamics is strongly influenced by Brownian rotation, the artificial Janus nanomotors show bursts of linear ballistic motion resulting in enhanced diffusion.

Dynamic inclusion complexes of metal nanoparticles inside nanocups.

Host-guest inclusion complexes are abundant in molecular systems and of fundamental importance in living organisms. Realizing a colloidal analogue of a molecular dynamic inclusion complex is challenging because inorganic nanoparticles (NPs) with a well-defined cavity and portal are difficult to synthesize in high yield and with good structural fidelity. Herein, a generic strategy towards the fabrication of dynamic 1:1 inclusion complexes of metal nanoparticles inside oxide nanocups with high yield (>70%) and regiospecificity (>90%) by means of a reactive double Janus nanoparticle intermediate is reported. Experimental evidence confirms that the inclusion complexes are formed by a kinetically controlled mechanism involving a delicate interplay between bipolar galvanic corrosion and alloying-dealloying oxidation. Release of the NP guest from the nanocups can be efficiently triggered by an external stimulus.

Hybrid nanocolloids with programmed three-dimensional shape and material composition.

Tuning the optical, electromagnetic and mechanical properties of a material requires simultaneous control over its composition and shape. This is particularly challenging for complex structures at the nanoscale because surface-energy minimization generally causes small structures to be highly symmetric. Here we combine low-temperature shadow deposition with nanoscale patterning to realize nanocolloids with anisotropic three-dimensional shapes, feature sizes down to 20 nm and a wide choice of materials. We demonstrate the versatility of the fabrication scheme by growing three-dimensional hybrid nanostructures that contain several functional materials with the lowest possible symmetry, and by fabricating hundreds of billions of plasmonic nanohelices, which we use as chiral metafluids with record circular dichroism and tunable chiroptical properties.

Hybrid plasmonic aerogel with tunable hierarchical pores for size-selective multiplexed detection of VOCs with ultrahigh sensitivity.

Sensitive and rapid identification of volatile organic compounds (VOCs) at ppm level with complex composition is vital in various fields ranging from respiratory diagnosis to environmental safety. Herein, we demonstrate a SERS gas sensor with size-selective and multiplexed identification capabilities for VOCs by executing the pre-enrichment strategy. In particular, the macro-mesoporous structure of graphene aerogel and micropores of metal-organic frameworks (MOFs) significantly improved the enrichment capacity (1.68 mmol/g for toluene) of various VOCs near the plasmonic hotspots. On the other hand, molecular MOFs-based filters with different pore sizes could be realized by adjusting the ligands to exclude undesired interfering molecules in various detection environments. Combining these merits, graphene/AuNPs@ZIF-8 aerogel gas sensor exhibited outstanding label-free sensitivity (up to 0.1 ppm toluene) and high stability (RSD=14.8%, after 45 days storage at room temperature for 10 cycles) and allowed simultaneous identification of multiple VOCs in a single SERS measurement with high accuracy (error < 7.2%). We visualize that this work will tackle the dilemma between sensitivity and detection efficiency of gas sensors and will inspire the design of next-generation SERS technology for selective and multiplexed detection of VOCs.

A paper-based dual functional biosensor for safe and user-friendly point-of-care urine analysis.

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 µA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.

Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular Level.

Two-dimensional transition metal carbon/nitrides (MXenes) are promising candidates to revolutionize next-generation wearable sensors as high-performance surface-enhanced Raman scattering (SERS) substrates. However, low sensitivity of pure MXene nanosheets and weak binding force or uncontrolled in situ growth of plasmonic nanoparticles on hybrid MXene composites limit their progress toward universal and reliable sensors. Herein, we designed and manufactured a highly sensitive, structurally stable wearable SERS sensor by in situ fabrication of plasmonic nanostructures on the flexible TiVC membranes via the maximization of chemically reducing sites using alkaline treatment. DFT calculations and experimental characterization demonstrated that the hydroxyl functional groups on the surface of MXenes can facilitate the reduction of metal precursors and the nucleation of gold nanoparticles (AuNPs) and can be covalently attached to AuNPs. Thus, the fabricated flexible TiVC-OH-Au sensor satisfied the rigorous mechanical requirements for wearable sensors. In addition, combining the electromagnetic (EM) enhancement from dense AuNPs formed by the activation of nucleation sites and charge transfer (CT) between target molecule and substrate induced by the abundant DOS near the Fermi level of TiVC, the fabricated sensor exhibits ultrasensitivity, long-term stability, good signal repeatability, and excellent mechanical durability. Moreover, the proof-of-concept application of the wearable SERS sensor in sweat sensing was demonstrated to monitor the content of nicotine, methotrexate, nikethamide, and 6-acetylmorphine in sweat at the molecular level, which was an important step toward the universality and practicality of the wearable sensing technology.

Ultrasensitive colorimetric detection of creatinine via its dual binding affinity for silver nanoparticles and silver ions.

Creatinine is an important biomarker for the diagnosis of chronic kidney disease (CKD). Recently, it has been reported that the concentration of salivary creatinine correlates well with the concentration of serum creatinine, which makes the former useful for the development of non-invasive and point-of-care (POC) detection for CKD diagnosis. However, there exists a technical challenge in the rapid detection of salivary creatinine at low concentrations of 3-18 µM when using the current kidney function test strips as well as the traditional methods employed in hospitals. Herein, we demonstrate a simple, sensitive colorimetric assay for the detection of creatinine with a limit-of-detection (LOD) down to the nanomolar level. Our approach utilises the dual binding affinity of creatinine for citrate-capped silver nanoparticles (Ag NPs) and Ag(i) ions, which can trigger the aggregation of Ag NPs and thus lead to the colour change of a sample. The quantitative detection of creatinine was achieved using UV-Vis spectroscopy with a LOD of 6.9 nM in artificial saliva and a linear dynamic range of 0.01-0.06 µM. This method holds promise to be further developed into a POC platform for the CKD diagnosis.

Modulation of redox reactivity of resazurin through host-guest complexation with Cucurbit[n]uril (n = 7, 8).

Resazurin (Alamar Blue, RZ) is a widely utilized fluorescent probe for biological sensing, whose fluorescent intensity can be modulated by changing its redox states; thereby, electrochemical reactivity of RZ is of significance when designing a sensing assay. Herein, we report novel two-way electrochemical reactivity modulation of RZ using host-guest complexation with rigid molecular containers cucurbit[n]uril (CBn, n = 7, 8). The complexation between CBn and RZ is confirmed by 1H NMR measurements and supported by computational simulation, and the binding constants are determined via UV-vis titration. Notably, the voltametric data highlights that the redox reactivity of RZ can be activated or deactivated upon encapsulation by CB8 or CB7, respectively. This two-way reactivity modulation is hypothesized to be mediated by the difference in cavity volume that favors or hinders the approach of water molecules to the encapsulated reaction center during the reduction process. Despite the similar cavity size to CB, molecular containers such as cyclodextrins (CDs) exhibit considerably weaker modulation effects. Our approach can potentially be applied to other redox processes that involve proton transfer, and open new possibilities in supramolecular electrochemistry.

Plasmonic Coupling of Au Nanoclusters on a Flexible MXene/Graphene Oxide Fiber for Ultrasensitive SERS Sensing.

High sensitivity, good signal repeatability, and facile fabrication of flexible surface enhanced Raman scattering (SERS) substrates are common pursuits of researchers for the detection of probe molecules in a complex environment. However, fragile adhesion between the noble-metal nanoparticles and substrate material, low selectivity, and complex fabrication process on a large scale limit SERS technology for wide-ranging applications. Herein, we propose a scalable and cost-effective strategy to a fabricate sensitive and mechanically stable flexible Ti3C2Tx MXene@graphene oxide/Au nanoclusters (MG/AuNCs) fiber SERS substrate from wet spinning and subsequent in situ reduction processes. The use of MG fiber provides good flexibility (114 MPa) and charge transfer enhancement (chemical mechanism, CM) for a SERS sensor and allows further in situ growth of AuNCs on its surface to build highly sensitive hot spots (electromagnetic mechanism, EM), promoting the durability and SERS performance of the substrate in complex environments. Therefore, the formed flexible MG/AuNCs-1 fiber exhibits a low detection limit of 1 × 10-11 M with a 2.01 × 109 enhancement factor (EFexp), signal repeatability (RSD = 9.80%), and time retention (remains 75% after 90 days of storage) for R6G molecules. Furthermore, the l-cysteine-modified MG/AuNCs-1 fiber realized the trace and selective detection of trinitrotoluene (TNT) molecules (0.1 µM) via Meisenheimer complex formation, even by sampling the TNT molecules at a fingerprint or sample bag. These findings fill the gap in the large-scale fabrication of high-performance 2D materials/precious-metal particle composite SERS substrates, with the expectation of pushing flexible SERS sensors toward wider applications.

Triple-enhanced Raman scattering sensors from flexible MXene/Au nanocubes platform via attenuating the coffee ring effect.

Developing substrates that combine sensitivity and signal stability is a major challenge in surface enhanced Raman scattering (SERS) research. Herein, we present a flexible triple-enhanced Raman Scattering MXene/Au nanocubes (AuNCs) sensor fabricated by selective filtration of Ti3C2Tx MXene/AuNCs hybrid on the Ti3C2Tx MXene membrane and subsequent treatment with 1H,1H,2H,2H-perfluoro-octyltriethoxysilane (FOTS). The resultant superhydrophobic MXene/AuNCs-FOTS membrane not only provides the SERS substrate with environmental stability, but also imparts analyte enrichment to enhance the sensitivity (LOD = 1 × 10-14 M) and reliability (RSD = 6.41%) for Rhodamine 6G (R6G) molecules owing to the attenuation of the coffee ring effect. Moreover, the triple enhancement mechanism of combining plasmonic coupling enhancement from plasmonic coupling (EM) of nearby AuNCs at lateral and longitudinal direction of MXene/AuNCs-FOTS membrane, charge transfer (CT) from Ti3C2Tx MXene and target molecules and analyte enrichment function provides the substrate with excellent SERS performance (EF = 3.19 × 109), and allows efficient quantification of biomarkers in urine. This work could provide new insights into MXenes as building blocks for high-performance substrates and fill existing gaps in SERS techniques.

Supramolecular Click Chemistry for Surface Modification of Quantum Dots Mediated by Cucurbit[7]uril.

Cucurbiturils (CBs), barrel-shaped macrocyclic molecules, are capable of self-assembling at the surface of nanomaterials in their native state, via their carbonyl-ringed portals. However, the symmetrical two-portal structure typically leads to aggregated nanomaterials. We demonstrate that fluorescent quantum dot (QD) aggregates linked with CBs can be broken-up, retaining CBs adsorbed at their surface, via inclusion of guests in the CB cavity. Simultaneously, the QD surface is modified by a functional tail on the guest, thus the high affinity host-guest binding (logKa > 9) enables a non-covalent, click-like modification of the nanoparticles in aqueous solution. We achieved excellent modification efficiency in several functional QD conjugates as protein labels. Inclusion of weaker-binding guests (logKa = 4-6) enables subsequent displacement with stronger binders, realising modular switchable surface chemistries. Our general "hook-and-eye" approach to host-guest chemistry at nanomaterial interfaces will lead to divergent routes for nano-architectures with rich functionalities for theranostics and photonics in aqueous systems.

A facile synthesis of dynamic supramolecular aggregates of cucurbit[n]uril (n=5-8) capped with gold nanoparticles in aqueous media.

Supramolecular capping of cucurbit[n]uril (CB[n]), where n=5-8, by narrowly dispersed gold nanoparticles has been achieved through a facile synthetic route with metastable gold nanoparticles as a labile intermediate. The resultant assemblies were stable in solution, and were found to form dynamic aggregates consisting of a controllable ratio of singly and doubly capped CB[n]. The stability of the system was attributed to the presence of sodium cations bound on the vacant carbonyl portals of the singly capped CB[n] molecules. These dynamically capped CB[n] systems can find potential use in a range of applications varying from ultrasensitive multiplexed in situ sensing to photocatalysis.

Triply triggered doxorubicin release from supramolecular nanocontainers.

The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.

Modulating the reaction pathway of phenyl diazonium ions using host-guest complexation with cucurbit[7]uril.

Aryl diazonium ions are known to be an important intermediate in the divergent synthesis of azo compounds and substituted aromatics. The presence of more than one electrophilic center in a diazonium ion could lead to undesirable side reactions during a synthesis. Herein, we report that the electrophilic α-carbon on a phenyl diazonium [PhN2]+ ion can be selectively deactivated upon host-guest complexation with cucurbit[7]uril (CB7) in aqueous media, achieving a ∼60-fold increase in the half-life of [PhN2]+. Notably, however, the electrophilic nitrogen of the encapsulated diazonium ion remains active towards diazo coupling with strong nucleophiles, allowing the formation of azo compounds using a two-month-old aqueous solution of [CB7-PhN2]+. Our supramolecular approach can open new possibilities for the reactive chemistry of organic molecules in aqueous media.

Supramolecular Hydrogels: Design Strategies and Contemporary Biomedical Applications.

Self-assembly of supramolecular hydrogels is driven by dynamic, non-covalent interactions between molecules. Considerable research effort has been exerted to fabricate and optimise supramolecular hydrogels that display shear-thinning, self-healing, and reversibility, in order to develop materials for biomedical applications. This review provides a detailed overview of the chemistry behind the dynamic physicochemical interactions that sustain hydrogel formation (hydrogen bonding, hydrophobic interactions, ionic interactions, metal-ligand coordination, and host-guest interactions). Novel design strategies and methodologies to create supramolecular hydrogels are highlighted, which offer promise for a wide range of applications, specifically drug delivery, wound healing, tissue engineering and 3D bioprinting. To conclude, future prospects are briefly discussed, and consideration given to the steps required to ultimately bring these biomaterials into clinical settings.

Pseudobullous pilomatricoma: A rare variant of pilomatricoma.

Pilomatricoma (PM; calcifying epithelioma of Malherbe) is an uncommon adnexal tumour originating from the matrix of the hair follicles. Bullous appearance is a rare variant of PM, and its pathogenesis remains unclear. Here, we present a case of a 17-year-old girl with a pseudobullous PM on the right shoulder. Lymphatic dilatation and collagen disorder were histopathologically observed in this case, which may provide clues to elucidate the pathogenesis of pseudobullous PM.