Abstract Mimicking Nature's polymeric protein architectures by designing hosts with binding cavities screened from bulk solvent is a promising approach to achieving anion recognition in competitive media. Accomplishing this, however, can be synthetically demanding. Herein we present a synthetically tractable approach, by directly incorporating potent supramolecular anion‐receptive motifs into a polymeric scaffold, tuneable through a judicious selection of the co‐monomer. A comprehensive analysis of anion recognition and sensing is demonstrated with redox‐active, halogen bonding polymeric hosts. Notably, the polymeric hosts consistently outperform their monomeric analogues, with especially large halide binding enhancements of ca. 50‐fold observed in aqueous‐organic solvent mixtures. These binding enhancements are rationalised by the generation and presentation of low dielectric constant binding microenvironments from which there is appreciable solvent exclusion.
Mimicking nature’s biopolymeric protein architectures by designing hosts with binding cavities shielded from the bulk solvent environment is a promising approach to achieving anion recognition in competitive protic media. Accomplishing this, however, can be synthetically demanding. Herein we present a more synthetically tractable approach, by directly incorporating potent supramolecular anion recognition motifs into a polymeric scaffold, which can be engineered through a judicious selection of the co-monomer. This is demonstrated through a comprehensive analysis of anion recognition and sensing with redox-active, halogen bonding (XB) polymeric host systems. Notably, the polymeric hosts consistently outperform their monomeric analogues, with especially large halide anion binding enhancements by up to 50-fold observed in aqueous-organic solvent mixtures. These enhancements are rationalised by a consideration of generated low dielectric constant binding microenvironments from which there is appreciable solvent exclusion. This approach is applicable to a range of hosts and targets, enabling recognition and sensing in highly polar media, otherwise unattainable with the monomeric units alone.
Abstract The ability of natural enzymes to regulate their guest binding affinities and preferences through the use of co‐ligands which alter the features of the binding site is fundamental to biological homeostatic control. Herein, the rarely exploited orthosteric control of guest binding is demonstrated using neutral halogen bonding [2]rotaxanes, in which a chemical stimulus (acid) interacting with the interlocked host binding site switches the host's native guest preference from metal cations to anions. When neutral, the rotaxanes exhibit pronounced transition metal cation affinity and comparatively weak anion binding properties. However, the addition of acid attenuates the rotaxanes’ ability to coordinate cations, while concurrently enabling strong binding of halides through charge assisted halogen bonding and hydrogen bonding interactions in competitive aqueous solvent media. The appendage of a fluorescent anthracene reporter group to the rotaxane framework also enables diagnostic sensory responses to cation/anion binding.
The development of real-life applicable ion sensors, in particular those capable of repeat use and long-term monitoring, remains a formidable challenge. Herein, we demonstrate, in a proof-of-concept, the real-time voltammetric sensing of anions under continuous flow at electroactive anion receptive halogen bonding (XB) and hydrogen bonding (HB) ferrocene-isophthalamide-(iodo)triazole interfaces. Upon exposure to anions, the cathodic perturbations of the ferrocene redox-transducer are monitored by repeat square-wave voltammetry (SWV) cycling and peak fitting of the voltammograms by a custom-written MATLAB script. This enables the facile and automated data processing of thousands of SW scans and is associated with an over one order-of-magnitude improvement in LODs. In addition, this improved analysis enables tuning of the measurement parameters such that high temporal resolution can be achieved. More generally, this novel flow methodology is extendable to a variety of other analytes, including cations, and presents an important step towards translation of voltammetric ion sensors from laboratory to real-world applications.
The spike protein (S) of SARS-CoV-2 is the major target of neutralizing antibodies and vaccines. Antibodies that target the receptor-binding domain (RBD) of S have high potency in preventing viral infection. The ongoing evolution of SARS-CoV-2, especially mutations occurring in the RBD of new variants, has severely challenged the development of neutralizing antibodies and vaccines. Here, a murine monoclonal antibody (mAb) designated E77 is reported which engages the prototype RBD with high affinity and potently neutralizes SARS-CoV-2 pseudoviruses. However, the capability of E77 to bind RBDs vanishes upon encountering variants of concern (VOCs) which carry the N501Y mutation, such as Alpha, Beta, Gamma and Omicron, in contrast to its performance with the Delta variant. To explain the discrepancy, cryo-electron microscopy was used to analyze the structure of an RBD–E77 Fab complex, which reveals that the binding site of E77 on RBD belongs to the RBD-1 epitope, which largely overlaps with the binding site of human angiotensin-converting enzyme 2 (hACE2). Both the heavy chain and the light chain of E77 interact extensively with RBD and contribute to the strong binding of RBD. E77 employs CDRL1 to engage Asn501 of RBD and the Asn-to-Tyr mutation could generate steric hindrance, abolishing the binding. In sum, the data provide the landscape for an in-depth understanding of immune escape of VOCs and rational antibody engineering against emerging variants of SARS-CoV-2.
A family of cationic halogen bonding [2]rotaxanes have been synthesisedviaan active-metal template synthetic strategy.1H NMR spectroscopic anion titration investigations reveal these interlocked host systems recognize halides selectively over oxoanions in aqueous–organic solvent media. Furthermore, systematically modulating the rigidity and size of the rotaxanes’ anion binding cavitiesviametal complexation, as well as by varying the number of halogen bond-donor groups in the axle component, was found to dramatically influence halide anion selectivity.
The shield tunnel structure is susceptible to seismic damage in liquefied slippage areas. In order to evaluate the seismic performance of shield tunnel structures in liquefied slippage areas, a refined beam-spring shield tunnel model based on the generalized response displacement method is established. The feasibility of the generalized response displacement method is discussed. Based on an engineering case study, a 4.8km shield tunnel model is established to investigate the longitudinal seismic response of the shield tunnel in the liquefied slippage area. The numerical results show that for the focus area: (1) The generalized response displacement method can effectively consider the influences of topographic effects and site liquefaction slippage on the longitudinal seismic response of the shield tunnel. (2) The site slippage is harmful to the safety of the tunnel structure, as it may cause a large longitudinal opening width at the ring intersegment as well as sudden changes in section tension and pressure. (3) The bending moment variation curve and the acceleration amplification factor curve along the tunnel axis are consistent with the site topography, and the curves show obvious abrupt changes in the liquefied slippage areas.
The liquefaction-induced lateral spreading of the fluvial terraces can cause tremendous physical damage to the natural and built environments in the lower reaches of Yangtze River. This paper presents an integrated nonlinear site response analyses method to characterize the large-scale lateral spreading behavior in the wide river valley of Yangtze River at the scale of several kilometers, incorporating the main features such as the spatial variability of liquefiable deposit, the liquefaction initiation and cyclic mobility at the post liquefaction stage and the geometric nonlinearity induced by the extensively large deformation. In particular, the large-deformation behavior in the numerical model is simulated by the plasticity-based model at the element level and the ALE method at the model mesh level. The key factors influencing lateral spreading behavior are investigated, involving the ground motion characteristics, the slope angle of fluvial terraces, and the spatial variability of site condition. The numerical results indicate significant spatial variation characteristics of the lateral spreading of the fluvial terraces, triggered in the slightly inclined slope. Three generation stages of lateral spreading could be identified in the time-history curve of lateral displacement, i.e. swing stage, slip stage and creep stage, respectively. Finally, the model performance of the proposed modelling method is evaluated against the widely-used empirical formula, and the difference between each other is interpreted, which provides new insights into the mechanism of liquefaction-induced lateral spreading of the fluvial terraces in the wide river valley.
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