Covalent Reaction Research Articles

Synthesis of Magnetic Attapulgite Nanoparticles Via a Novel Surface Covalent Reaction Method and its Application in the Magnetic Solid Phase Extraction.

In this study, the attapulgite nanoparticle was immobilized on the surface of magnetic nanoparticle Fe3O4 via a novel surface covalent reaction method for the magnetic solid phase extraction (MSPE) for the first time. The surface covalent reaction method has the advantages of controllable steps, and can make the magnetic attapulgite nanoparticle (MANP) have good homogeneity and high stability. Field emission scanning electron microscopy, equipped with an energy dispersive spectrometer, Nitrogen adsorption BET, X-ray diffraction and Fourier transform infrared spectroscopy were applied to characterize the prepared MANP, confirming that the attapulgite nanoparticle could be effectively immobilized on the surface of magnetic nanoparticle Fe3O4 via covalent reactions. Under optimal conditions of the MSPE experiment based on the MANP, the limits of detection were found to be 10ng/mL for melamine and 3ng/mL for cyromazine with a relative standard deviation < 10% by a high-performance liquid chromatography system. Meanwhile, 0.1mg/mL melamine in milk and 0.1mg/mL cyromazine in cucumber can also be detected according to our MSPE procedure. More importantly, the MANP still has good magnetism and enrichment efficiency after several decades of use. These results showed that the MANP prepared by our method is a kind of promising material for the MSPE.

Reactivities of acrylamide warheads toward cysteine targets: a QM/ML approach to covalent inhibitor design.

Covalent inhibition offers many advantages over non-covalent inhibition, but covalent warhead reactivity must be carefully balanced to maintain potency while avoiding unwanted side effects. While warhead reactivities are commonly measured with assays, a computational model to predict warhead reactivities could be useful for several aspects of the covalent inhibitor design process. Studies have shown correlations between covalent warhead reactivities and quantum mechanic (QM) properties that describe important aspects of the covalent reaction mechanism. However, the models from these studies are often linear regression equations and can have limitations associated with their usage. Applications of machine learning (ML) models to predict covalent warhead reactivities with QM descriptors are not extensively seen in the literature. This study uses QM descriptors, calculated at different levels of theory, to train ML models to predict reactivities of covalent acrylamide warheads. The QM/ML models are compared with linear regression models built upon the same QM descriptors and with ML models trained on structure-based features like Morgan fingerprints and RDKit descriptors. Experiments show that the QM/ML models outperform the linear regression models and the structure-based ML models, and literature test sets demonstrate the power of the QM/ML models to predict reactivities of unseen acrylamide warhead scaffolds. Ultimately, these QM/ML models are effective, computationally feasible tools that can expedite the design of new covalent inhibitors.

Matrix curing and stress field development around fiber during the solvent evaporation-induced repolymerization of recycling composites

When recycling fiber-reinforced composites using depolymerized polymer solutions, oligomers reconnect through covalent bond exchange reactions (BERs), which ultimately forms a crosslinked network with mechanical properties comparable to those of virgin materials. This process offers exciting opportunities for the primary recycling of engineering composites, but it is intricately influenced by a few material and process parameters, such as heating temperature, duration, and fiber volume fractions. These parameters collectively determine the matrix's curing degree and the evolution of stress fields around the fiber, which are significant factors determining the quality and mechanical performance of recycled composites. This study introduces a diffusion-reaction-mechanics finite-element computational model to examine the solvent-induced repolymerization process in recycling composites. The model predicts the matrix curing degree, residual stress development around the fiber, and the composite's mechanical properties, aligning with experimental results. Parametric computational studies are then conducted to assess the influences of temperature, fiber content, solvent diffusivity, and the reactivity of BERs. The objective is to identify material and processing conditions that ensure efficient composite recycling while minimizing the development of residual stress. Overall, this study enhances our understanding of the mechanisms behind composite recycling using organic solvents and provides valuable insights for industrial stakeholders looking to optimize processing conditions and advance the commercialization and widespread adoption of this innovative recycling technique.

Switching between Nonisoenergetic Dynamic Covalent Reactions Using Host-Guest Chemistry.

CO2 reacts with simple amines in the presence of water to generate dynamic combinatorial libraries of majority (i.e., ammonium carbamates) and minority (i.e., ammonium carbonates) nonisoenergetic covalent adducts. Over the past two decades, our laboratory has reported on a new class of cavitands, namely, dyn[n]arenes, from which a polyanionic macrocycle is a highly efficient receptor for linear polyammoniums that forms [2]pseudorotaxanes in water at neutral pH. Herein, we demonstrate that the formation of [2]pseudorotaxanes shifts the equilibrium of CO2 capture by polyamines in water toward the quasi-exclusive formation of carbonate adducts, providing the first example of a switch between two competitive and reversible covalent processes triggered by host-guest interactions. In addition, this supramolecular approach to CO2 capture exhibits enhanced capture efficiency by increasing the state of protonation of complexed vs uncomplexed polyamines. Altogether, we report here that a templating approach can divert the outcome of two reversible covalent chemistries involving nucleophilic additions and acid-base reactions, challenging therefore the common knowledge that noncovalent and covalent bonds operate in separate energy frames.

14C-Isotope Use to Quantify Covalent Reactions between Flavor Compounds and β-Lactoglobulin.

A 14C-based method was developed to study the rate and extent of covalent bond formation between β-lactoglobulin and three model flavor compounds: a ketone (2-undecanone UDO), an aldehyde (decanal DAL), an isothiocyanate (2-phenylethyl isothiocyanate PEITC), and an unreactive "methods blank" (decane DEC). Aqueous protein solutions with one of the 14C-labeled model flavor compounds were placed in water baths at 25, 45, and 65 °C for 4 weeks measuring the amount of flavor: protein reaction at 1, 3, 7, 14, 21, and 28 days. UDO showed lowest reactivity (max of 0.9% of added compound reacted), DAL (max of 16.4% reacted), and PEITC (max of 71.8% reacted). All compounds showed a rapid initial reaction rate which slowed after ca. 7 days. It appears that only PEITC (at 65 °C) saturated all potential protein-reactive sites over the storage period.

3D Printed Room Temperature Phosphorescence Materials Enabled by Edible Natural Konjac Glucomannan.

Shaping room temperature phosphorescence (RTP) materials into 3D bodies is important for stereoscopic optoelectronic displays but remains challenging due to their poor processability and mechanical properties. Here, konjac glucomannan (KGM) is employed to anchor arylboronic acids with various π conjugations via a facile B─O covalent reaction to afford printable inks, using which full-color high-fidelity 3D RTP objects with high mechanical strength can be obtained via direct ink writing-based 3D printing and freeze-drying. The doubly rigid structure supplied by the synergy of hydrogen bonding and B─O covalent bonding can protect the triplet excitons; thus, the prepared 3D RTP object shows a striking lifetime of 2.14 s. The printed counterparts are successfully used for 3D anti-counterfeiting and can be recycled and reprinted nondestructively by dissolving in water. This success expands the scope of printable 3D luminescent materials, providing an eco-friendly platform for the additive manufacturing of sophisticated 3D RTP architectures.

Comparison of Non-Covalent and Covalent Interactions between Lactoferrin and Chlorogenic Acid.

Adding polyphenols to improve the absorption of functional proteins has become a hot topic. Chlorogenic acid is a natural plant polyphenol with anti-inflammatory, antioxidant, and anticancer properties. Bovine lactoferrin is known for its immunomodulatory, anticancer, antibacterial, and iron-chelating properties. Therefore, the non-covalent binding of chlorogenic acid (CA) and bovine lactoferrin (BLF) with different concentrations under neutral conditions was studied. CA was grafted onto lactoferrin molecules by laccase catalysis, free radical grafting, and alkali treatment. The formation mechanism of non-covalent and covalent complexes of CA-BLF was analyzed by experimental test and theoretical prediction. Compared with the control BLF, the secondary structure of BLF in the non-covalent complex was rearranged and unfolded to provide more active sites, the tertiary structure of the covalent conjugate was changed, and the amino group of the protein participated in the covalent reaction. After adding CA, the covalent conjugates have better functional activity. These lactoferrin-polyphenol couplings can carry various bioactive compounds to create milk-based delivery systems for encapsulation.

A Minimalistic Covalent Bond-Forming Chemical Reaction Cycle that Consumes Adenosine Diphosphate.

The development of synthetic active matter requires the ability to design materials capable of harnessing energy from a source to carry out work. Nature achieves this using chemical reaction cycles in which energy released from an exergonic chemical reaction is used to drive biochemical processes. Although many chemically fuelled synthetic reaction cycles that control transient responses, such as self-assembly, have been reported, the generally high complexity of the reported systems hampers a full understanding of how the available chemical energy is actually exploited by these systems. This lack of understanding is a limiting factor in the design of chemically fuelled active matter. Here, we report a minimalistic synthetic responsive reaction cycle in which adenosine diphosphate (ADP) triggers the formation of a catalyst for its own hydrolysis. This establishes an interdependence between the concentrations of the network components resulting in the transient formation of the catalyst. The network is sufficiently simple that all kinetic and thermodynamic parameters governing its behaviour can be characterised, allowing kinetic models to be built that simulate the progress of reactions within the network. While the current network does not enable the ADP-hydrolysis reaction to populate a non-equilibrium composition, these models provide insight into the way the network dissipates energy. Furthermore, essential design principles are revealed for constructing driven systems, in which the network composition is driven away from equilibrium through the consumption of chemical energy.

Structural transformation investigations of δ to α manganese dioxides: Phosphate sorption and its mechanism

The elevation of environmental phosphate levels can negatively impact both the natural environment and human health. To address this issue, a series of MnO2 sorbents were investigated in this study. A facile one-pot synthesis method was employed to fabricate distinct morphologies and crystalline structures by controlling the hydrothermal duration. As the hydrothermal duration was prolonged, the samples demonstrated a pronounced enhancement of stability and crystalline phases, along with a corresponding increase in structural oxygen vacancies. A series of sorption performance tests were conducted, including pH effect, sorption isotherm, sorption kinetics, co-existing ions and sorption–desorption cycles experiments. It was revealed that manganese dissolution, the surface charge of the sorbents, and the phosphate species at different pH values collectively influenced the sorption process. The sorbent α-MnO2-120 h, with the highest oxygen vacancy ratio, exhibited the best sorption performance towards phosphate ions, with the maximum sorption capacity at pH 7. The highest removal rate and kd value were 82.63 % and 2.29 × 103 mL g−1, respectively, at the initial concentration of 30.7 mg PO4 g−1. The α-MnO2-120 h sorbent exhibited excellent selectivity in the presence of NO3−, SO42−, CO32−, and SiO32−. Furthermore, the regenerated material exhibited only a 6 % decrease in phosphate removal efficiency after five cycles, with no structural changes observed. A novel mechanism was proposed, highlighting the dominance of covalent chemical reactions in the sorption process. In particular, the participation of oxygen vacancies in sorbents contributed to enhancing the effective removal of phosphate ions. Overall, this study successfully demonstrated that synthesized α-MnO2 is a promising sorbent for phosphate removal.

Dynamic Covalent Synthesis Applied to Optoelectronic and Energy Materials: Design, Applications and Limitations

AbstractDynamic Covalent Chemistry, consisting in the use of dynamic covalent bonds (DCBs) to create complex objects by working at the thermodynamic equilibrium, has undeniable advantages for the preparation of conjugated systems with tailored optoelectronic properties for organic electronics. Chemists can combine simple building blocks with simple functional groups of appropriate geometry, structure and stoichiometry to build multidimensional conjugated architectures. Dynamic covalent reactions are often precious metal‐free, generate little to no side products and are very efficient. DCBs however afford sensitive materials, and consequently a balance needs to be found between the ease of synthesis, the stability and the performances. The dynamicity of the target materials hence can considerably reduce their applicability in organic electronics where strongly stable materials are needed, but opens the door to stimuli‐responsive behaviour and recyclability. A way to overcome dynamicity issues is to lock DCBs, but often at the cost of decreased conjugation. In this review, we will highlight how DCBs are employed to prepare functional optoelectronically active materials, such as discrete molecules, polymers or covalent organic frameworks, applied in fields ranging from organic light‐emitting diodes and solar cells to organic batteries and transistors. We will also discuss their limitations, benefits and the current challenges to overcome.

Effects of additional ring-fusion site on dual reactivity based dynamic covalent chemistry

Tautomers are widespread in organic chemistry, and their unique reactivity allows diverse transformations. In this work, the incorporation of nearby amide ring-fusion site offered a versatile platform for controlling dual reactivity based dynamic covalent chemistry (DCC) of aldehyde ring-chain tautomers. A suite of 2-formylbenzosulfonamide derived tautomers were prepared, and the intramolecular ring-chain equilibrium and intermolecular dynamic covalent reactions along the underlying mechanistic foundation were investigated. By regulating the substituent electronic effect and solvent effect, ring-chain tautomerization equilibrium was readily regulated in solution. The adjacent amide NH participates in intramolecular hydrogen bonding, as revealed by crystal analysis. Furthermore, the addition of acid and the change of solvent allowed turning on/off the intramolecular cyclization from the amide group to create fused ring scaffolds. Finally, the reversible covalent reactions with amine nucleophile reagents maintained the intermolecular reactivity successfully. The molecular and pathway diversity reported herein sets the scene for future design and applications.

Computational Investigation of the Covalent Inhibition Mechanism of Bruton's Tyrosine Kinase by Ibrutinib.

Covalent inhibitors represent a promising class of therapeutic compounds. Nonetheless, rationally designing covalent inhibitors to achieve a right balance between selectivity and reactivity remains extremely challenging. To better understand the covalent binding mechanism, a computational study is carried out using the irreversible covalent inhibitor of Bruton tyrosine kinase (BTK) ibrutinib as an example. A multi-μs classical molecular dynamics trajectory of the unlinked inhibitor is generated to explore the fluctuations of the compound associated with the kinase binding pocket. Then, the reaction pathway leading to the formation of the covalent bond with the cysteine residue at position 481 via a Michael addition is determined using the string method in collective variables on the basis of hybrid quantum mechanical-molecular mechanical (QM/MM) simulations. The reaction pathway shows a strong correlation between the covalent bond formation and the protonation/deprotonation events taking place sequentially in the covalent inhibition reaction, consistent with a 3-step reaction with transient thiolate and enolates intermediate states. Two possible atomistic mechanisms affecting deprotonation/protonation events from the thiolate to the enolate intermediate were observed: a highly correlated direct pathway involving proton transfer to the Cα of the acrylamide warhead from the cysteine involving one or a few water molecules and a more indirect pathway involving a long-lived enolate intermediate state following the escape of the proton to the bulk solution. The results are compared with experiments by simulating the long-time kinetics of the reaction using kinetic modeling.

A Soy Protein-Based Film Based on Chemical Treatment and Microcrystalline Cellulose Reinforcement Obtained from Corn Husk Byproducts.

Developing an environmentally friendly soy protein-based film that offers excellent performance has garnered considerable interest while also posing a significant challenge. Herein, we propose the strategy of covalent and noncovalent cross-linking to improve the mechanical properties of the films. First, chemical denaturation was carried out under the combined action of sodium sulfite, sodium dodecyl sulfate, sodium hydroxide, and urea to reshape the structure of the protein to improve the solubility of protein and release active groups. Then, microcrystalline cellulose (MCC) derived from low-cost agro-industrial byproducts (corn husk) was employed to balance the covalent cross-linking reaction between proteins and the noncovalent reaction between MCC and protein. The results indicate that the structure and properties of the soy protein-based films were modified and improved through chemical treatment in conjunction with biomass enhancement. It is concluded that the addition of 1% MCC improves the tensile strength, elastic modulus, water solubility, and water vapor permeability of "MCC-1%" by 64.7, 75.9, 22.7, and 12.9%, respectively. Additionally, the resulting film of "MCC-1%" exhibits better resistance to thermal degradation and improved thermo-stability. However, the elongation at break decreased by increasing the addition of MCC. Thus, this work may provide a simple and affordable approach to preparing a high-performing soy protein-based film.

Discovery of Covalent Lead Compounds Targeting 3CL Protease with a Lateral Interactions Spiking Neural Network.

Covalent drugs exhibit advantages in that noncovalent drugs cannot match, and covalent docking is an important method for screening covalent lead compounds. However, it is difficult for covalent docking to screen covalent compounds on a large scale because covalent docking requires determination of the covalent reaction type of the compound. Here, we propose to use deep learning of a lateral interactions spiking neural network to construct a covalent lead compound screening model to quickly screen covalent lead compounds. We used the 3CL protease (3CL Pro) of SARS-CoV-2 as the screen target and constructed two classification models based on LISNN to predict the covalent binding and inhibitory activity of compounds. The two classification models were trained on the covalent complex data set targeting cysteine (Cys) and the compound inhibitory activity data set targeting 3CL Pro, respected, with good prediction accuracy (ACC > 0.9). We then screened the screening compound library with 6 covalent binding screening models and 12 inhibitory activity screening models. We tested the inhibitory activity of the 32 compounds, and the best compound inhibited SARS-CoV-2 3CL Pro with an IC50 value of 369.5 nM. Further assay implied that dithiothreitol can affect the inhibitory activity of the compound to 3CL Pro, indicating that the compound may covalently bind 3CL Pro. The selectivity test showed that the compound had good target selectivity to 3CL Pro over cathepsin L. These correlation assays can prove the rationality of the covalent lead compound screening model. Finally, covalent docking was performed to demonstrate the binding conformation of the compound with 3CL Pro. The source code can be obtained from the GitHub repository (https://github.com/guzh970630/Screen_Covalent_Compound_by_LISNN).

Abstract 7213: Tumor targeted activation of an attenuated exatecan protodrug through Click Chemistry demonstrates efficacy in murine tumor studies

Abstract Shasqi is advancing the Click Activated Protodrugs Against Cancer (CAPAC®) platform based on click chemistry, a Nobel Prize winning technology. The platform is modular and comprises 1) an activator that target specific antigens, and 2) inert cancer drugs, protodrugs, which are selectively activated at tumors via click chemistry. The CAPAC technology separates the tumor targeting function from the payload and re-unites them at the tumor creating the flexibility to optimize activity while limiting toxicity during preclinical and clinical development. The modularity of the platform enables the rapid development of new therapies as well as unlocking unique treatment benefits such as tunable combinations and payload cycling. We envision that CAPAC will expand the scope of potential targets, widen the therapeutic window, and enhance the safety of locally activated cancer therapeutics. Here, we demonstrate the efficacy and safety of our exatecan protodrug (SQP07) used with intratumorally injected activators. The activators, tetrazine-modified sodium hyaluronate biopolymer(s), are injected at the tumor site and followed by a systemic dose of SQP07, a trans-cyclooctene (TCO)-modified protodrug of exatecan (Exa). An efficient covalent reaction between tetrazine and TCO moieties releases active Exa at the tumor. In vitro cytotoxicity studies showed that SQP07 activated with tetrazine was effective against mouse and human tumor cell lines (MC38, CT26, EMT6 and NCI-N87); SQP07 without activator had potency attenuated by 60-133 fold. In vivo tumor distribution and activity of SQP07 with the intratumoral biopolymer activators was evaluated in an NCI-N87 gastric cancer xenograft model. Female C.B-17 SCID mice received a single intravenous dose of vehicle (10% HPCD), Exa (50 mg/kg) or biopolymer (40 or 100 μL intratumorally) followed by SQP07 or SQP07 alone (50 mg/kg Exa mol equivalent). 1 hour after biopolymer + SQP07 treatment, activated Exa was highly concentrated in the tumor and stroma. This led to tumor regression in animals up to 40 days, performing significantly better than the free drug cytotoxic, Exa alone. Similarly, median survival with biopolymer + SQP07 was higher (&amp;gt;81 days) compared to Exa (68.5 days). Toxicity, measured as body weight loss, was comparable (~5%) and transient between Exa and biopolymer + SQP07. SQP07 alone treatment without the biopolymer was not differentiated from the vehicle control. These data show that the CAPAC platform, which separates the targeting agent from the payload, is an effective way to administer cytotoxic therapies systemically. Additional work with other tumor models, different biopolymers and the SQP07 protodrug is ongoing. Citation Format: Sangeetha Srinivasan, Stefanie Wagner, George Coricor, Tri-Hung Nguyen, Jesse M. McFarland, José M. Mejía Oneto. Tumor targeted activation of an attenuated exatecan protodrug through Click Chemistry demonstrates efficacy in murine tumor studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7213.

Abstract 7214: A click chemistry-based HER2 targeting agent activates a decoupled MMAE payload making it highly differentiated in efficacy and safety than ADCs

Abstract Shasqi is advancing the Click Activated Protodrugs Against Cancer (CAPAC®) platform based on click chemistry, a Nobel Prize winning technology. The platform is modular and comprises of 1) an activator that targets specific antigens, and 2) inert cancer drugs, protodrugs, which are selectively activated at tumors via click chemistry. The CAPAC technology separates the tumor targeting function from the payload and reunites them at the tumor creating the flexibility to optimize activity while limiting toxicity during preclinical and clinical development. The modularity of the platform enables the rapid development of new therapies as well as unlocking unique treatment benefits such as tunable combinations and payload cycling. We envision that CAPAC will expand the scope of potential targets, widen the activity window of antibody drug conjugates (ADCs). Here we compare a HER2-targeting activator + a monomethyl auristatin E (MMAE) payload with an ADC that binds the same target and carries the same payload, as well as other targeting formats. The activator SQT01 is composed of a HER2-binding Fab conjugated with tetrazines (Tz). The protodrug SQP22 is formed by coupling trans-cyclooctene (TCO, with a releasable linker) to MMAE, a cytotoxic spindle poison. An efficient covalent reaction between tetrazine and TCO moieties releases active MMAE at the tumor. Mice bearing human NCI-N87 HER2+ tumor were treated with 1) SQT01, 2) a non-binding isotype Fab-Tz, or 3) saline. After 18 h, all mice received either vehicle (10% HPCD), SQP22 protodrug, a non-releasable MMAE TCO-protodrug analog of SQP22, or a di-peptide-containing TCO-protodrug analog. We also tested CAPAC’s approach with SQT06 (a full-length IgG trastuzumab-Tz conjugate) that was followed by an SQP22 dose after 4 days. The dosing of SQP22 with the Fab-Tz and IgG-Tz is timed to allow for systemic clearance of the targeting activator. Fabs have a shorter half-life than IgG, so we dosed SQP22 at 18 h after SQT01 instead of the 4-day timepoint with SQT06. To allow comparisons with ADCs, additional groups received a single dose of commercially available disitamab vedotin (DV) or a HER2-Fab-vedotin. SQT01+SQP22 induced a strong tumor growth inhibition comparable to SQT06+SQP22, but significantly better than DV, and SQT01+non-releasable protodrug analog. Dosing with SQT01 with a protease cleavable dipeptide-TCO protodrug analog or a molar equivalent dose of HER2-Fab-vedotin were highly toxic and intolerable. Based on preclinical observations, SQT01+SQP22 was safe and tolerated, and there was no observed body weight loss. These data demonstrate that the CAPAC platform, which separates the targeting agent from the payload, provides a clear benefit in terms of safety and efficacy compared with small or large format proteins with the classic fixed construct of ADCs (e.g. a fixed drug to antibody ratio). Citation Format: Sangeetha Srinivasan, Stefanie Wagner, George Coricor, Jesse M. McFarland, Tri-Hung Nguyen, José M. Mejía Oneto. A click chemistry-based HER2 targeting agent activates a decoupled MMAE payload making it highly differentiated in efficacy and safety than ADCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7214.

Ultrasound-enhanced covalent reaction of gliadin: the inhibition of antigenicity and its potential mechanisms.

Wheat proteins can be divided into water/salt-soluble protein (albumin/globulin) and water/salt-insoluble protein (gliadins and glutenins (Glu)) according to solubility. Gliadins (Glia) are one of the major allergens in wheat. The inhibition of Glia antigenicity by conventional processing techniques was not satisfactory. In this study, free radical oxidation was used to induce covalent reactions. The effects of covalent reactions by high-intensity ultrasound (HIU) of different powers was compared. The enhancement of covalent grafting effectiveness between gliadin and (-)-epigallo-catechin 3-gallate (EGCG) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry and Folin-Ciocalteu tests. HIU caused protein deconvolution and disrupted the intrastrand disulfide bonds that maintain the tertiary structure, causing a shift in the side chain structure, as proved by Fourier, fluorescence and Raman spectroscopic analysis. Comparatively, the antigenic response of the conjugates formed in the sonication environment was significantly weaker, while these conjugates were more readily hydrolyzed and less antigenic during simulated gastrointestinal fluid digestion. HIU-enhanced free radical oxidation caused further transformation of the spatial structure of Glia, which hid or destroyed the antigenic epitope, effectively inhibiting protein antigenicity. This study widened the application of polyphenol modification in the inhibition of wheat allergens. © 2024 Society of Chemical Industry.

High-strength and ultra-tough supramolecular polyamide spider silk fibers assembled via specific covalent and reversible hydrogen bonds

Achieving ultra-high tensile strength and exceptional toughness is a longstanding goal for structural materials. However, previous attempts using covalent and non-covalent bonds have failed, leading to the belief that these two properties are mutually exclusive. Consequently, commercial fibers have been forced to compromise between tensile strength and toughness, as seen in the differences between nylon and Kevlar. To address this challenge, we drew inspiration from the disparate tensile strength and toughness of nylon and Kevlar, both of which are polyamide fibers, and developed an innovative approach that combines specific intermolecular disulfide bonds and reversible hydrogen bonds to create ultra-strong and ultra-tough polyamide spider silk fibers. Our resulting Supramolecular polyamide spider silk, which has a maximum molecular weight of 1084 kDa, exhibits high tensile strength (1180 MPa) and extraordinary toughness (433 MJ/m3), surpassing Kevlar's toughness 8-fold. This breakthrough presents a new opportunity for the sustainable development of spider silk as an environmentally friendly alternative to synthetic commercial fibers, as spider silk is composed of amino acids. Future research could explore the use of these techniques and fundamental knowledge to develop other super materials in various mechanical fields, with the potential to improve people's lives in many ways. Statement of significance• By emulating synthetic commercial fibers such as nylon and polyethylene, we have successfully produced supramolecular-weight polyamide spider silk fibers with a molecular weight of 1084 kDa through a unique covalent bond-mediated linear polymerization reaction of spider silk protein molecules. This greatly surpasses the previous record of a maximum molecular weight of 556 kDa. • We obtained supramolecular polyamide spider silk fibers with both high-tensile strength and toughness. The stress at break is 1180 MPa, and the toughness is 8 times that of kevlar, reaching 433 MJ/m3. • Our results challenge the notion that it is impossible to manufacture fibers with both ultra-high tensile strength and ultra-toughness, and provide theoretical guidance for developing environmentally friendly and sustainable structural materials that meet industrial needs.

Aggregable gold nanoparticles for cancer photothermal therapy.

Photothermal therapy (PTT) is an important non-invasive cancer treatment method. Enhancing the photothermal conversion efficiency (PCE) of photothermal agents (PTAs) and prolonging their tumor accumulation and retention are effective strategies to enhance the efficiency of cancer PTT. Recently, tremendous progress has been made in developing stimuli-responsive aggregable gold nanoparticles as effective PTAs for PTT. In this review, we discuss the chemical principles underlying gold nanoparticle aggregation and highlight the progress in gold nanoparticle aggregation triggered by different stimuli, especially tumor microenvironment-related factors, for cancer PTT. Covalent condensation reactions, click cycloaddition reactions, chelation reactions, and Au-S bonding, as well as non-covalent electrostatic interactions, hydrophobic interactions, hydrogen bonding, and van der Waals forces play key roles in the aggregation of gold nanoparticles. Enzymes, pH, reactive oxygen species, small molecules, salts, and light drive the occurrence of gold nanoparticle aggregation. Targeted aggregation of gold nanoparticles prolongs tumor accumulation and retention of PTAs and improves PCE, resulting in enhanced tumor PTT. Moreover, the major challenges of aggregable gold nanoparticles as PTAs are pointed out and the promising applications are also prospected at the end. With the deepening of research, we expect aggregable gold nanoparticles to become essential PTAs for tumor therapy.

Tetrazine cyclized peptides for one-bead-one-compound library: Synthesis and sequencing.

While most FDA-approved peptide drugs are cyclic, robust cyclization chemistry of peptides and the deconvolution of the cyclic peptide sequences using tandem mass spectrometry render cyclic peptide drug discovery difficult. In this chapter, the protocol for the successful synthesis of tetrazine-linked cyclic peptide library in solid phase, which shows both robust cyclization and easy sequence deconvolution, is described. The protocol for the linearization and cleavage of cyclic peptides from the solid phase by simple UV light irradiation, followed by accurate sequencing using tandem mass spectrometry, is described. We describe the troubleshooting for this dithiol bis-arylation reaction and for the successful cleavage of the aryl cyclic peptide into linear form. This method for efficient solid-phase macrocyclization can be used for the rapid production of loop-based peptides and screening for inhibition of protein-protein interactions, by using the covalent inverse electron-demand Diels Alder reaction to supplement the non-covalent interaction between a protein and its peptide binder, isolating highly selective peptides in the process.