Reversible Interactions Research Articles

C-H functionalization through benzylic deprotonation with π-coordination or cation-π-interactions.

Benzylic C-H functionalization is a valuable tool to make complex aromatic molecules from simple, readily available alkylbenzenes. While methods that involve benzylic radicals or cations generated by hydrogen atom transfer or oxidation have been well demonstrated, they often require oxidative conditions. In contrast, deprotonation methods offer a complementary approach to transform benzylic C-H bonds through a benzylic carbanion generated by deprotonation. Electrophilic transition metal complexes acidify benzylic protons upon π-coordination to the phenyl ring of substrates, facilitating deprotonation by stabilizing the corresponding benzylic carbanion. Cation-complexes with group(I) metals also acidify benzylic C-H bonds. These approaches enable a significant expansion of the scope and diversity of alkylarenes with various electrophilic reagents. In this review, we discuss the development of benzylic functionalization through deprotonation of η6-arene complexes of transition-metals and cation-π interactions with group(I) metals, as well as progress made in catalysis through reversible arene-metal interactions.

Tailored Supramolecular Additives to Control the Crystallization Process and Morphology of MAPbI3.

Perovskite films feature unique optoelectronic properties, rendering them promising for electronic devices. The properties depend on the morphology on a broad range of length scales from nanometers to millimeters, influenced by a variety of factors. However, controlling the morphology is challenging. A tailored supramolecular additive, N, N'-bis(2-aminoethyl) terephthalamide is developed to control the intermediate and perovskite crystallization of methyl ammonium lead iodide (MAPbI3) and enhance the thermal and moisture stability in the final film. Reversible coordinative interactions of the carbonyl groups with Pb2+ ions via Lewis acid-base adduct and subsequent ion-ion interactions of the peripheral ammonium groups with the perovskite grain boundaries are combined which is stabilized by a strong hydrogen bonding pattern formed between the amide moieties of the additive molecules. Adding low amounts of this additive to the precursor solution significantly decelerates the structure formation and systematically reduces the crystallite size. Slower growth of the intermediate phases and the incorporation of the additive to the grain boundary is observed with multiple time-resolved techniques. Evidence for the formation of single-molecule interlayers between the MAPbI3 crystals and the presence of directed supramolecular interaction between additive molecules is shown. Transferability of this approach to other perovskites is anticipated, paving the way to improved processing control and stability.

Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates.

The advent of biomacromolecules antagonizing vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). However, frequent intravitreal injections of these biomacromolecules impose an enormous burden on patients and create a massive workload for healthcare providers. This causes patients to abandon therapy, ultimately leading to progressive and irreversible vision loss. In order to address this unmet clinical need, a noninvasive treatment for nAMD is developed. An optimized cell-penetrating peptide derivative, bxyPenetratin (bxyWP), is used to non-covalently complex with the anti-VEGF protein aflibercept (AFL) via reversible hydrophobic interaction. The interaction is crucial for AFL delivery, neither impairing the affinity of AFL to pathological VEGF, nor being interfered by endogenous proteins in tear fluids. AFL/bxyWP eye drops exhibit prolonged retention on the eye and excellent absorption into the posterior ocular segment following topical administration, with significant drug distribution to the retina and choroid. In a laser-induced choroidal neovascularization model on cynomolgus monkeys, AFL/bxyWP eye drops efficiently reduce lesion size and leakage comparable to conventional intravitreal injection of AFL. These results suggest that AFL/bxyWP eye drops are feasible self-administered treatment for neovascular retinal diseases and potentially become a substitute for intravitreal injections.

Biocompatible autonomous self-healing PVA-CS/TA hydrogels based on hydrogen bonding and electrostatic interaction

The biocompatible autonomous self-healing hydrogels have great potential in biomedical applications. However, the fairly weak tensile strength of the hydrogels seriously hinders their application. Here, we introduced chitosan (CS) into the polyvinyl alcohol (PVA)-tannic acid (TA) hydrogel and investigated the effects of the CS content, as CS can not only form reversible H bonds with PVA and TA but also form reversible electrostatic interactions with TA. Since the bond energy of electrostatic interaction is much stronger than that of the H bond, the tensile strength and self-healing properties of PVA-TA hydrogel can potentially be improved by adding the CS. The results suggested that when the PVA content and the total content of CS and TA were fixed (PVA: 30 wt.%; CS + TA: 3 wt.%) and the CS content was increased to 1 wt.%, the tensile strength of the PVA-CS/TA hydrogel could be up to 447 kPa, and the self-healing efficiency remained at 84% in 2 h. Compared with the reported self-healing hydrogels with similar biocompatibility and self-healing properties, whose tensile strength is usually less than 300 kPa, the PVA-CS/TA hydrogel prepared here shows a significant improvement in the tensile strength.

An electrochemical microsensor of the SARS-CoV-2 nucleocapsid protein based on a surface-imprinted acupuncture needle.

A novel electrochemical microsensor was constructed on a traditional acupuncture needle (AN) and used to monitor a biomarker of the SARS-CoV-2-N protein. The reversible interaction of the borate bond between the cis-diol in this glycoprotein and the phenylboronic acid in 4-mercaptophenylboronic acid (4-MPBA) was accomplished. This interaction was applied to anchor the SARS-CoV-2-N protein onto 4-MPBA, which was covalently self-assemblied onto electrodeposited AuNPs by the S-Au bond. Meldola blue was then electropolymerized around the protein template. After the template had eluted, three-dimensional nanocavities complementary to the protein were generated within the polymeldola blue (pMB) layer. Interestingly, nanocavities could play a channel role for the electron-transfer of outer [Fe(CN)6]3-/4-, and the signal of the electrochemical probe could be hindered after recombination of the SARS-CoV-2-N protein, which lays a platform for the detection of this biomarker. After optimizing the influencing factors, the prepared microsensor exhibited a linear range of 0.1-1000 ng mL-1 with a low detection limit of 0.01 ng mL-1 (S/N = 3). In particular, the sensing ability was dramatically affected by the thickness correlative factor for the polymer matrix. A suitable thickness is effective for sensing the signals, which corresponds to the behavior of the surface-imprinted polymer. The microsensor showed comparatively high sensitivity and selectivity and practically detected the SARS-CoV-2-N protein in the serum sample, which is of scientific significance for the development of electrochemical microsensors and acupuncture.

A synthetic protein-level neural network in mammalian cells.

Artificial neural networks provide a powerful paradigm for nonbiological information processing. To understand whether similar principles could enable computation within living cells, we combined de novo-designed protein heterodimers and engineered viral proteases to implement a synthetic protein circuit that performs winner-take-all neural network classification. This "perceptein" circuit combines weighted input summation through reversible binding interactions with self-activation and mutual inhibition through irreversible proteolytic cleavage. These interactions collectively generate a large repertoire of distinct protein species stemming from up to eight coexpressed starting protein species. The complete system achieves multi-output signal classification with tunable decision boundaries in mammalian cells and can be used to conditionally control cell death. These results demonstrate how engineered protein-based networks can enable programmable signal classification in living cells.

Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner

GABAergic synapses critically modulate neuronal excitability, and plastic changes in inhibitory synaptic strength require reversible interactions between GABAA receptors (GABAARs) and their postsynaptic anchor gephyrin. Inhibitory long-term potentiation (LTP) depends on the postsynaptic recruitment of gephyrin and GABAARs, whereas the neurotransmitter GABA can induce synaptic removal of GABAARs. However, the mechanisms and players underlying plastic adaptation of synaptic strength are incompletely understood. Here we show that neurobeachin (Nbea), a receptor trafficking protein, is a component of inhibitory synapses, interacts with gephyrin and regulates the downscaling of inhibitory synaptic transmission. We found that the recruitment of Nbea to GABAergic synapses is activity-dependent and that Nbea regulates GABAAR internalization in a protein kinase A (PKA)-dependent manner. In heterozygous neurons lacking one Nbea allele, re-expression of Nbea but not expression of a PKA binding-deficient Nbea mutant rescued the internalization of GABAARs. Our data suggest a mechanism by which Nbea mediates PKA anchoring at inhibitory postsynaptic sites to downregulate GABAergic transmission. They emphasize the importance of kinase positioning in the regulation of synaptic strength.

DEM-Based Micro–Macro Assessment of Reverse Fault-Foundation Interaction Enhanced by a Strong Inclined Wall

DEM-Based Micro–Macro Assessment of Reverse Fault-Foundation Interaction Enhanced by a Strong Inclined Wall

Facile Preparation of Polymerizable Deep Eutectic Solvents Under Mild Conditions for Multisensory Ionic Skins.

Polymerizable deep eutectic solvents (PDESs) have emerged as promising building blocks for next-generation eutectic gels, offering new opportunities for the development of advanced electronic devices. Traditional PDES fabrication typically involves heating and extended processing time. In this study, a facile method where a solid-solid mixture of lithium bis(trifluoromethane) sulfonimide (LiTFSI) and acrylamide (AAm) rapidly forms a PDES at room temperature, significantly simplifying the ionogel preparation is presented. By combining this PDES withanothersystem,comprising3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate (SBMA) and ethylene glycol (EG), an eutectic gel is successfully fabricated with exceptional mechanical and conductive properties. This gel exhibits a fracture stress of 0.8MPa, fracture energy of 3.7kJ m-2, adhesion strength of 60kPa, transmittance over 90%, high conductivity (0.113 S m-1), and an outstanding temperature tolerance ranged from -50 to 50 °C. Notably, the absence of chemical crosslinkers and the presence of reversible interactions such as hydrogen bonding and ion-dipole electrostatic forces impart excellent self-healing capabilities. These combined features position the gel a promising candidate for multisensory ionic skins, capable of detecting pressure, temperature, humidity, and sweat. This work pioneers the rapid, mild-condition synthesis of PDESs, paving the way for new techniques in ionic skin development.

Semi-intrinsic self-healing epoxy coating using ionic liquid and super absorbent polymer

In recent years, there has been a growing interest in self-healing materials due to their capacity to mend micro to nano-scale damages, enhancing longevity and reducing maintenance costs associated with equipment repair. This study introduces a self-healing epoxy-based polymeric coating achieved through the incorporation of a reversible ionic liquid (IL) network and a superabsorbent polymer (SAP) in a straightforward one-pot blending process. The reversible interaction between the hydroxyl groups of epoxy and ionic groups initiates the healing process under dry conditions. Moreover, the addition of SAP enhances the system's ability to initiate healing in wet and moist environments. Evaluation of the healing capability through SEM images reveals complete healing after 14 h in dry conditions and 24 h in wet conditions. Additionally, a series of physical and thermal tests were conducted to assess the effects of increasing IL concentration and curing agent in the epoxy system. For instance, the modified sample with 8 % weight of IL exhibited a 63 % higher elongation break compared to pure epoxy. It is believed that this straightforward one-pot composition holds significant potential for various applications, including the construction and automotive industries.

Discovery of Chalcone Derivatives as Bifunctional Molecules with Anti-SARS-CoV-2 and Anti-inflammatory Activities.

Danshensu extracted with traditional Chinese medicine Salvia miltiorrhiza has a wide range of bioactivities. Danshensu containing a catechol moiety has a moderate inhibitory effect on SARS-CoV-2 3CLpro (IC50 = 2.2 μM) by a reversible covalent interaction and exhibits good anti-inflammatory activity. To enhance the inhibitory activity, we introduced Michael receptors into the side chain of danshensu as a possible covalent warhead and blocked the covalent binding sites of catechol moiety to yield chalcone derivatives. The resulting chalcone derivatives, A4 and A7, were found to inhibit SARS-CoV-2 3CLpro in vitro with IC50 values of 83.2 and 261.3 nM, respectively. Furthermore, A4 and A7 inhibit viral replication in the SARS-CoV-2 replicon system with EC50 values of 19.9 and 11.7 μM, respectively. Time-dependent inhibition experiment and mass spectrometry show that A4 acted as a noncovalent mixed inhibitor, while A7 likely binds covalently at Cys145. The interaction mechanism between SARS-CoV-2 3CLpro and A4 or A7 was characterized by molecular docking studies. Additionally, both A4 and A7 demonstrated potent anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. These promising results suggest that chalcone derivatives A4 and A7 can serve as bifunctional molecules with both antivirus and anti-inflammatory properties.

Extremely Ultrahigh Stretchable Starch‐Based Hydrogels with Continuous Hydrogen Bonding

AbstractNatural polysaccharides‐based hydrogels have drawn extensive attention yet have been plagued by less desirable stretchability due to their inherent nature. Here, ultra‐stretchable starch‐based hydrogels (amylopectin/polyacrylamide, AAM) are developed by constructing reversible intramolecular physical interactions. This strategy endows the hydrogel with exceedingly ultrahigh deformation due to a continuous hydrogen bonding network. It can be stretched from less than 0.5 to >300 cm without breakage that the elongation exceeds 600 times the original length. The elongation collected by the universal testing machine reaches up to 36 000% without breakage outperforming previous reports and demonstrating extraordinary stretchability. Furthermore, an interwoven structure of hydrogen bonding interaction and trace covalent bonds make the stress of hydrogel reach 0.28 MPa, accompanied by an ultra‐high strain of 22 500% and significant toughness (47 MJ·m−3). The hydrogel displays high transparency (≈93%), low‐temperature resistance, moisturizing property, and extraordinary interfacial adhesion property. Intriguingly, the aqueous precursor can act as inks to prepare various forms of hydrogel within minutes through the facile writing or drawing method. This hydrogel verifies strong potential in both fields of human motion sensor (After long‐term or low‐temperature conditions) and energy storage. This study will facilitate the progress of ultra‐stretchable or multifunctional hydrogels.

Toughening Vitrimers Based on Dioxaborolane Metathesis through Introducing a Reversible Secondary Interaction

Toughening Vitrimers Based on Dioxaborolane Metathesis through Introducing a Reversible Secondary Interaction

Highly Elastic, Fatigue-Resistant, and Antifreezing MXene Functionalized Organohydrogels as Flexible Pressure Sensors for Human Motion Monitoring.

Conductive organohydrogels-based flexible pressure sensors have gained considerable attention in health monitoring, artificial skin, and human-computer interaction due to their excellent biocompatibility, wearability, and versatility. However, hydrogels' unsatisfactory mechanical and unstable electrical properties hinder their comprehensive application. Herein, an elastic, fatigue-resistant, and antifreezing poly(vinyl alcohol) (PVA)/lipoic acid (LA) organohydrogel with a double-network structure and reversible cross-linking interactions has been designed, and MXene as a conductive filler is functionalized into organohydrogel to further enhance the diverse sensing performance of flexible pressure sensors. The as-fabricated MXene-based PVA/LA organohydrogels (PLBM) exhibit stable fatigue resistance for over 450 cycles under 40% compressive strain, excellent elasticity, antifreezing properties (<-20 °C), and degradability. Furthermore, the pressure sensors based on the PLBM organohydrogels show a fast response time (62 ms), high sensitivity (S = 0.0402 kPa-1), and excellent stability (over 1000 cycles). The exceptional performance enables the sensors to monitor human movements, such as joint flexion and throat swallowing. Moreover, the sensors integrating with the one-dimensional convolutional neural networks and the long-short-term memory networks deep learning algorithms have been developed to recognize letters with a 93.75% accuracy, representing enormous potential in monitoring human motion and human-computer interaction.

Electrochemically Switchable Sulfurized Polyacrylonitrile for Controllable Recovery of Copper in Wastewater Based on Reversible Adsorption/Desorption Regulation.

Within the context of circular economy and industrial ecology, adsorption offers an effective manner for recycling resources from wastewater, but controllable desorption remains a challenge. Inspired by metal-thiol binding and reversible thiol-disulfide redox transformation in biological systems, this study reports the development of a reversible adsorption/desorption (RAD) system for controllable recovery of copper based on electrochemically switchable sulfurized polyacrylonitrile (SPAN). Density functional theory calculations offered theoretical prediction for the formation of S-Cu bonds and reversible weak interaction between S-S bonds and Cu2+. The SPAN anchored onto titanium suboxide ceramic foam (SPAN@TiSO) could regulate Cu2+ adsorption/desorption stimulated by the electrode potential, indicated by the adsorption capacity of 243.3 mg g-1 (30 min) at 0.2 V vs SHE and a desorption efficiency of 98.4% (5 min) at 0.8 V vs SHE. Electrochemical analysis revealed that the reversible redox transformation of S-S/-S- groups in SPAN was responsible for selective adsorption and rapid desorption in response to the electrode potential. This study provides a proof-of-concept demonstration of an electrochemically switchable polymer to build up a reversible RAD system for controllable recovery of heavy metals in wastewater, making value-added resource recovery more efficient, more intelligent, and more sustainable.

Elimination of mutagenic contaminants from water using cellulose bearing ferrous-phthalocyanine

BackgroundWe previously investigated methods for separating mutagenic contaminants from aqueous solutions using cellulose-bearing covalently bound trisulfo-Cu-phthalocyanine (blue cotton and blue rayon). Mutagenic contaminants with three or more fused aromatic rings in their structures were adsorbed onto blue cotton and rayon. Since Cu-phthalocyanine is considered an unsuitable absorption ligand for byproducts of water chlorination, such as 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (Mutagen X or MX), we investigated the development of a new material for the elimination of MX from aqueous solvents.ResultsWe selected green cellulose powder bearing ferrous phthalocyanine (FePh), hereafter referred to as green cellulose or GP, as the candidate material. GP is composed of cationized cellulose (white cellulose, WP) and FePh tetracarboxylic acid. The mutagenicity of MX dissolved in buffer or dimethyl sulfoxide (DMSO) solution significantly decreased after treatment with GP. The effects of GP on the elimination of MX from the solvent were very close to being expired after 70 cycles of repeated adsorption of the same GP, and the capacity of GP for MX removal was estimated to be exhausted after 120 cycles of repeated adsorption based on the extrapolation of the obtained result; thus, the interacting ligands on GP may be saturated after complete MX adsorption. The mutagenicity of MX dissolved in aqueous buffer significantly decreased after treatment at pH7.4 but not at pH 4.0. Since MX is dissociated to be the anionic form at pH 6 or higher, the negative charge of MX in the buffer at pH 7.4 may interact with the positive charge of ferrous ions in GP to create a linkage between MX and GP. After GP adsorbed MX, mutagenicity was extracted with water or acetonitrile and recovered in the eluent. Thus, the reversible interaction between MX and FePh may have caused adsorption of MX onto GP.ConclusionGP could be used as a new eliminator and recovery agent for MX in chlorinated drinking water. Developing new materials for the removal and recovery of agents for the detection of mutagenic contaminant-related chlorination in water is beneficial for environmental health.

Exploring the Interaction of Human α-Synuclein with Polyethylene Nanoplastics: Insights from Computational Modeling and Experimental Corroboration.

Plastics, particularly microplastics (MPs) and nanoplastics (NP), have become major environmental and health concerns due to their high chemical stability. The highly hydrophobic plastics enter living organisms through reversible interactions with biomolecules, forming biocoronas. Following recent reports on plastics breaching the blood-brain barrier, the binding behavior of human α-synuclein (hαSn) with polyethylene-based (PE) plastics was evaluated by using molecular dynamics simulations and experimental methods. The results provided three important findings: (i) hαSn transitions from an open helical to a compact conformation, enhancing intramolecular interactions, (ii) nonoxidized PE NPs (NPnonox) rapidly adsorb hαSn, as supported by experimental data from dynamic light scattering and adsorption isotherms, altering its structure, and (iii) the oxidized NP (NPox) failed to capture hαSn. These interactions were dominated by the N-terminal domain of hαSn, with major contributions from hydrophobic amino acids. These findings raise concerns about the potential pharmacological effects of NP-protein interactions on human health.

Performance of orange peels crosslinked β-cyclodextrin (OP-β-CD) to uptake lanthanum from water: Conventional adsorption studies and ultrasound-assisted desorption

Even though adsorption has been widely employed to recover rare earth elements such as lanthanum, desorption remains challenging since selectivity is often linked to strong adsorption forces. Herein we propose the grafting between orange peel (OP) wastes with beta-cyclodextrins (β-CD) for producing a highly reusable and stable adsorbent that allows the easy recovery of lanthanum in repeated cyclic runs. The morphological analysis confirmed that the OP-β-CD adsorbent was successfully functionalized with –OH groups, with β-CD grafting via citric acid expanding and stabilizing its structure. The pseudo-first-order model better represented the kinetics of lanthanum adsorption, while the isothermal behavior was better represented by the Langmuir model (qmax=95.79mgg−1), as shown by the thermodynamic analysis, which confirmed that the process was endothermic and spontaneous. The mechanism behind the efficiency of adsorption-desorption of lanthanum by OP-β-CD adsorbent was concluded to rely on: i) electrostatic and reversible interactions and ii) a driving force that increased as the amount of lanthanum increased in solution, leading to the formation of a monolayer. Around 95 % of lanthanum was desorbed using an ultrasound-assisted technique with citric acid, maintaining stable adsorption capacity for 5 cycles. In real matrices containing other rare earth elements and high calcium concentrations the removal exceeded 80 %. Thus, OP-β-CD's remarkable stability during desorption underscores its potential as a highly effective and sustainable solution for rare earth element recovery and removal.

Rational Design of Regenerable Amino-Functionalized Fluorescent Covalent Organic Framework for the Exclusive Detection of Mercury(II).

Goal-oriented development of novel covalent organic frameworks (COFs) to construct a sensing platform for highly toxic mercury (II, Hg2+) is of tremendous significance. Recently, numerous COFs with sulfur-based ligands were developed for Hg2+ monitoring; however, strong binding of Hg2+ by sulfur makes their regeneration very tough. Herein, we designed and developed an amino-functionalized fluorescent COF (COF-NH2) through facile postmodification for Hg2+ detection in which the π-conjugation skeleton is the signal reader and the nitrogen-based side is the highly selective Hg2+ receptor. More importantly, this nitrogen-based receptor permits the reversible binding of Hg2+. As a sensing platform, the outstanding performance of COF-NH2 for Hg2+ detection was reached with respect to high sensitivity with an ultralow detection of 15.3 nM, real-time response with rapid signal change of 10 s, and facile visualization with significant fluorescence color change. Expectedly, COF-NH2 obtained facile recycling which still shows excellent response performance toward Hg2+ after six cycles based on the reversible interaction between amino groups and Hg2+. Our work not only shows an attractive foreground of fluorescent COF for Hg2+ detection but also emphasizes the easy construction of novel COF materials via the rational introduction of metal ligands for the recognition of other metal ions.

Activation of muscle amine functional groups using eutectic mixture to enhance tissue adhesiveness of injectable, conductive and therapeutic granular hydrogel for diabetic ulcer regeneration

Herein, Polydopamine-modified microgels and microgels incorporated with superficial epoxy groups were synthesized and applied as precursors for the fabrication of four granular hydrogels. To enhance the tissue adhesiveness, a ternary deep eutectic solvent was synthesized to activate the muscle amine functional groups facilitating the formation of robust NC bonds at ambient conditions. At a certain shear rate of 10 s−1, hydrogel DMG displayed a viscosity of 9×103 Pa/s, representing the highest complex viscosity among the tested hydrogels primarily driven by quinone groups in PDA which enhanced reversible interactions, thereby increasing particle cohesion. Moreover, the intersection point escalating from about 4×103 to approximately 9×104 as the concentration of DMG increased from 0 % (for MG) to 70% (7D3MG) by weight. There was a decrease in adhesion strength from 0.45 ± 0.08 N in MG to 0.39 ± 0.16 N, 0.35± 0.18 N, and 0.33 ± 0.15 N for 3D7MG, 7D3MG, and DMG respectively, suggesting that MG was capable of forming numerous covalent bonds, thereby enhancing its adhesion to the substrate. The type of eutectic mixture affected the electrical conductivity and a very important point was the changes in resistance value with time. For MG catalyzed by [DES]AZG, the resistance increased only by 1.3 % (from 3.37 to 3.81 kΩ) at day 3 and 37.09 % (from 3.37 to 4.62 kΩ) at day 5. The 3D7MG hydrogel exhibited superior therapeutic efficacy toward diabetic wound regeneration. The proliferation index value for 3D7MG-[DES]AZG and 3D7MG-[DES]AG were calculated 42.3 % and 58.6 %, respectively, while the control group exhibited a lower value of 37.8 %.