Stable Bonds Research Articles

Artificial-Intelligence Bio-Inspired Peptide for Salivary Detection of SARS-CoV-2 in Electrochemical Biosensor Integrated with Machine Learning Algorithms

Developing affordable, rapid, and accurate biosensors is essential for SARS-CoV-2 surveillance and early detection. We created a bio-inspired peptide, using the SAGAPEP AI platform, for COVID-19 salivary diagnostics via a portable electrochemical device coupled to Machine Learning algorithms. SAGAPEP enabled molecular docking simulations against the SARS-CoV-2 Spike protein’s RBD, leading to the synthesis of Bio-Inspired Artificial Intelligence Peptide 1 (BIAI1). Molecular docking was used to confirm interactions between BIAI1 and SARS-CoV-2, and BIAI1 was functionalized on rhodamine-modified electrodes. Cyclic voltammetry (CV) using a [Fe(CN)6]3−/4 solution detected virus levels in saliva samples with and without SARS-CoV-2. Support vector machine (SVM)-based machine learning analyzed electrochemical data, enhancing sensitivity and specificity. Molecular docking revealed stable hydrogen bonds and electrostatic interactions with RBD, showing an average affinity of –250 kcal/mol. Our biosensor achieved 100% sensitivity, 80% specificity, and 90% accuracy for 1.8 × 10⁴ focus-forming units in infected saliva. Validation with COVID-19-positive and -negative samples using a neural network showed 90% sensitivity, specificity, and accuracy. This BIAI1-based electrochemical biosensor, integrated with machine learning, demonstrates a promising non-invasive, portable solution for COVID-19 screening and detection in saliva.

Nature and stability of the chemical bond in H3C-XHn (XHn = CH3, NH2, OH, F, Cl, Br, I).

We have quantum chemically analyzed the trends in bond dissociation enthalpy (BDE) of H3C-XHn single bonds (XHn = CH3, NH2, OH, F, Cl, Br, I) along three different dissociation pathways at ZORA-BLYP-D3(BJ)/TZ2P: (i) homolytic dissociation into H3C∙ + ∙XHn, (ii) heterolytic dissociation into H3C+ + -XHn, and (iii) heterolytic dissociation into H3C- + +XHn. The associated BDEs for the three pathways differ not only quantitatively but, in some cases, also in terms of opposite trends along the C-X series. Based on activation strain analyses and quantitative molecular orbital theory, we explain how these differences are caused by the profoundly different electronic structures of, and thus bonding mechanisms between, the resulting fragments in the three different dissociation pathways. We demonstrate that the nature and strength of a chemical bond are only fully defined when considering both (i) the molecule in which the bond exists and (ii) the fragments from which it forms or into which it dissociates.

Molecular Dynamics Simulation of Clay Mineral–Water Interfaces: Temperature-Dependent Structural, Dynamical, and Mechanical Properties

Water interacting with clay minerals—such as kaolinite, montmorillonite, and pyrophyllite—fundamentally governs their geotechnical and environmental functions, thereby influencing parameters such as retention, transport, and stability. Understanding the effects of temperature on water behavior within clay mineral interlayers is critical for predicting the performance of clay–water systems under dynamic environmental conditions. This study performed molecular dynamics simulations to investigate the structural, dynamical, and mechanical properties of interlayer water in three representative clay minerals over a temperature range of 298.15–363.15 K. Our analyses focused on mean squared displacement (MSD), density profiles, hydrogen bond dynamics, and stress distributions, thereby revealing the interaction between water structuring and thermal fluctuations. Results indicated distinct temperature-dependent changes in water diffusion and hydrogen bond stability, with montmorillonite consistently exhibiting enhanced water retention and steadier hydrogen bonding networks across the studied temperature spectrum. Density profiles highlighted pronounced confinement effects at lower temperatures that gradually diminish with increasing thermal energy. Concurrently, the stress distributions revealed the mechanical responses of clay–water interfaces, highlighting the interplay between thermal motion of water molecules and their interactions with the clay surfaces. These findings offer valuable insights into how temperature regulates water behavior in clay mineral interlayers and provide a foundation for advancing predictive modeling and the design of engineered systems in water-rich, thermally variable environments.

Preparation, characterization and antimicrobial activity of sodium carboxymethyl cellulose - based hydrogels by freeze-thaw method

This study evaluated the structural and functional properties of poly (vinyl alcohol)/sodium carboxymethyl cellulose (PVA/NaCMC) hydrogels synthesized via the freeze-thawing method using 1% acetic acid (AAc) and distilled water (Dw) as solvents. The results demonstrate that solvent choice and NaCMC concentration significantly influence hydrogel performance, particularly for wound dressings. PVA/NaCMC (AAc)-3.5% emerged as the optimal formulation, exhibiting superior antimicrobial activity, structural stability, and enhanced crosslinking, as evidenced by FT-IR, SEM, and TEM analyses. XRD confirmed higher crystallinity in the AAc-based hydrogel, while swelling tests showed greater water absorption in the Dw-based hydrogel, attributed to its looser network. Antimicrobial tests highlighted the broad-spectrum efficacy of PVA/NaCMC (AAc)-3.5%, inhibiting Gram-positive and Gram-negative bacteria and fungi due to acetic acid’s low pH and hydrogen bond stabilization. These findings emphasize the importance of solvent selection in designing hydrogels for wound care applications requiring infection prevention and structural integrity.

Comparative Phytochemistry of Polyacetylenes of the Genus Artemisia (Asteraceae): Compounds with High Biological Activities and Chemotaxonomic Significance

In spite of the many chemical reports on polyacetylenes of the genus Artemisia, combined conclusions regarding their distribution and biological functions are widely missing. The aim of the present review was to arrange the diversity of polyacetylenes in the genus following biogenetic aspects and group them together into characteristic structural types. The co-occurrence of the dehydrofalcarinol type with the aromatic capillen-isocoumarin type represents a characteristic biogenetic trend, clearly segregating species of the subgenus Dracunculus from those of the subgenera Artemisia and Absinthium, distinguished by the spiroketal enol ether and/or linear triyne type. Various accumulation trends toward specific structures additionally contribute to a more natural species grouping within the subgenera. Biological activities were reported for all four structural types, ranging from antifungal, insecticidal, nematicidal, and cytotoxic properties to allelopathic effects. Of particular interest were their remarkable cytotoxic potencies, from which the very high values of dehydrofalcarin-3,8-diol may be associated with the pronounced affinity of this type to form extremely stable bonds to proteins acting in signaling pathways. The aromatic acetylene capillin inhibited the viability of various tumor cells in a dose- and time-dependent manner. Its potent apoptosis-inducing activity was induced via the mitochondrial pathway. A group of spiroketal enol ethers was identified as inhibitors of PMA-induced superoxide generation. Among them, the epoxide of the isovalerate ester exhibited the highest potency. The ecological impact of acetylene formation was made apparent by the allelopathic effects of DME of the linear triyne type, and the aromatic capillen by inhibiting seed germination and growth of widespread weeds.

Combining Electrosorption and Electrochemical Reduction Mechanisms for Uranium Removal Using 1,2,3,4-Butane Tetracarboxylic Acid-Modified MIL-101: An In-Depth Exploration of Uranyl-Adsorbent Interactions.

Extracting uranium from nuclear wastewater is vital for environmental and human health protection. However, despite progress in uranium extraction, there remains a demand for an optimized adsorbent with improved capability, efficiency, and selectivity. To bridge this gap, 1,2,3,4-butane tetracarboxylic acid (BTCA)-modified MIL-101 was synthesized through a simple hydrothermal reaction between amino-modified MIL-101 (MIL-101-NH2) and BTCA. Density Functional Theory calculations validated the formation of stable coordination bonds and a hydrogen bond network, bolstering the adsorption capacity. To further enhance this capacity, the influence of an electric field on adsorption performance was investigated. Studies revealed that uranyl ion removal under an electric field involves both electrosorption and electroreduction pathways. This dual mechanism not only significantly increases the adsorption capacity from 221.1 mg g-1 to 331.4 mg g-1 but also improves the adsorption efficiency. These insights not only enhance our understanding of effective uranium removal but also foster the development of sustainable, ecofriendly technologies in the nuclear energy field.

Mechanistic insights and optimization of lignin depolymerization into aromatic monomers using vanadium-modified Dawson-type polyoxometalates.

Lignin, as the largest renewable aromatic resource, has significant opportunities for producing high-value products via catalytic depolymerization. However, its complex structure and stable chemical bonds present challenges to its transformation. This study explores the catalytic depolymerization of lignin to aromatic monomers by means of Dawson-type phosphomolybdovanadate polyoxometalates (POMs), understanding the underlying mechanisms. Furthermore, vanadium modification is employed to adjust the catalyst's oxidative and acidic properties, demonstrating that the vanadium content in Dawson-type POMs greatly influences monomer yield. The highest yield is achieved with H8P2Mo16V2O62 (V2). Optimal conditions include a reaction temperature of 150°C, 4h, an oxygen pressure of 1MPa, a methanol-to-water ratio of 8:2, and a mass ratio of the catalyst to the wood powder being 1:1, which leads to a total yield of aromatic monomers at 24%. POMs with high REDOX potential selectively oxidizes benzyl hydroxyl groups in lignin to benzyl carbonyl groups under the combined action of acidity and oxidation of polyacids. This weakens the βO4 bond and promotes CO bond cleavage. This approach, utilizing the tunable oxidative acidity of polyoxometalates to degrade lignin and produce various aromatic monomers, shows promising potential for lignin valorization and advancing a bio-economy based on lignocellulosic resources.

Antiviral Activity and Underlying Mechanism of Moslae herba Aqueous Extract for Treating SARS-CoV-2.

Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics to deal with the variants of SARS-CoV-2. Moslae herba (MH) is a herbal medicine credited with antiviral effects. This study aims to investigate the antiviral effects and the underlying mechanism of aqueous extract of Moslae herba (AEMH) for treating SARS-CoV-2. The in vitro anti-SARS-CoV-2 activity of AEMH was evaluated using cell viability and viral load. Component analysis was performed by HPLC-ESI-Q-TOF/MS. The connection between COVID-19 and AEMH was constructed by integrating network pharmacology and transcriptome profiles to seek the core targets. The components with antiviral activities were analyzed by molecular docking and in vitro pharmacological verification. AEMH exerted anti-SARS-CoV-2 effects by inhibiting viral replication and reducing cell death caused by infection (IC50 is 170 μg/mL for omicron strain). A total of 27 components were identified from AEMH. Through matching 119 intersection targets of 'disease and drug' with 1082 differentially expressed genes of COVID-19 patients, nine genes were screened. Of the nine, the PNP and TPI1 were identified as core targets as AEMH treatment significantly regulated the mRNA expression level of the two genes on infected cells. Three components, caffeic acid, luteolin, and rosmarinic acid, displayed antiviral activities in verification. Molecular docking also demonstrated they could form stable bonds with the core targets. This study explored the antiviral activity and possible mechanism of AEMH for treating SARS-CoV-2, which could provide basic data and reference for the clinical application of MH.

Study regarding the compatibility between cellulose acetate (CA) and ZnO nanoparticles in polymeric membrane structures using functionalized m-phenylenediamine

This study examines the effects of functionalized m-phenylenediamine (m-PDA-f) on the structure of cellulose acetate (CA) polymeric membranes enhanced with zinc oxide nanoparticles (ZnO). The membranes were prepared by dissolving cellulose acetate in an aprotic solvent, followed by a phase inversion process. The addition of m-PDA-f facilitates the formation of bridges between the cellulose acetate and ZnO nanoparticles. This is confirmed by FTIR analysis, which reveals a shift in the wavenumber of 3 to 5 cm⁻¹, highlighting an increase in the number of hydrogen bonds formed. Thermogravimetric analysis (TGA) confirms the enhanced stability of the membranes, with a significant increase in the thermal decomposition temperature: from 235 °C for pure cellulose acetate to 285 °C for the composite containing ZnO and the functionalized polymer. Differential scanning calorimetry (DSC) reveals lower enthalpy values for the membranes where mPDA-f is present alongside ZnO. Furthermore, the best hydrophilicity was observed in the CA – m-PDA-f – ZnO membranes, exhibiting a contact angle of 34 degrees for water droplets, compared to 51 degrees for the membrane without the functionalized polymer. This demonstrates an increase in compatibility between the polymer and the nanomaterial through the formation of additional stable bonds.

Chemical Space of Fluorinated Nucleosides/Nucleotides in Biomedical Research and Anticancer Drug Discovery

Fluorinated nucleos(t)ide drugs have proven to be successful chemotherapeutic agents in treating various cancers. The Food and Drug Administration (FDA) has approved several drugs that fit within the fluorinated nucleoside pharmacophore, and many more are either in preclinical development or clinical trials. The addition of fluorine atoms to nucleos(t)ides improves the metabolic stability of the glycosidic bond and, in certain instances, facilitates additional interactions of nucleons(t)ides with receptors. The insertion of fluorine either on sugar or the base of nucleos(t)ides proved to enhance the lipophilicity, pharmacokinetic, and pharmacodynamic properties. Overall, the fluorine atom feeds diverse advantages to the biological profile of nucleos(t)ide analogs by improving their drug-like properties and therapeutic potential. This review article covers the often-used fluorinating reagents in nucleoside chemistry, the clinical significance of [18F]-labeled nucleosides, the synthesis and anticancer activity of FDA-approved fluoro-nucleos(t)ide drugs, as well as clinical candidates, which are at various stages of clinical development as anticancer agents.

Stabilizing Lattice Oxygen of Bi2O3 by Interstitial Insertion of Indium for Efficient Formic Acid Electrosynthesis

Bismuth oxide (Bi2O3) emerges as a potent catalyst for converting CO2 to formic acid (HCOOH), leveraging its abundant lattice oxygen and the high activity of its Bi‐O bonds. Yet, its durability is usually impeded by the loss of lattice oxygen causing structure alteration and destabilized active bonds. Herein, we report an innovative approach via the interstitial incorporation of indium (In) into the Bi2O3, significantly enhancing bond stability and preserving lattice oxygen. The optimized In‐Bi2O3‐100 catalyst achieves over 90% Faradaic efficiency for HCOOH production across a wide potential range, in both H‐cells and flow cells, maintaining robust stability after 100 hours of continuous operation. In‐situ surface‐enhanced infrared absorption spectroscopy and theoretical calculations reveal that the interstitial In doping precisely tunes the adsorption of CO2* and OCHO* intermediate, facilitating rapid conversion. Further in‐situ Raman spectroscopy confirms the role of In bolstering the oxidized structure's stability within Bi2O3, critical for sustaining lattice oxygen during electrochemical CO2 reduction.

Stabilizing Lattice Oxygen of Bi2O3 by Interstitial Insertion of Indium for Efficient Formic Acid Electrosynthesis.

Bismuth oxide (Bi2O3) emerges as a potent catalyst for converting CO2 to formic acid (HCOOH), leveraging its abundant lattice oxygen and the high activity of its Bi-O bonds. Yet, its durability is usually impeded by the loss of lattice oxygen causing structure alteration and destabilized active bonds. Herein, we report an innovative approach via the interstitial incorporation of indium (In) into the Bi2O3, significantly enhancing bond stability and preserving lattice oxygen. The optimized In-Bi2O3-100 catalyst achieves over 90% Faradaic efficiency for HCOOH production across a wide potential range, in both H-cells and flow cells, maintaining robust stability after 100 hours of continuous operation. In-situ surface-enhanced infrared absorption spectroscopy and theoretical calculations reveal that the interstitial In doping precisely tunes the adsorption of CO2* and OCHO* intermediate, facilitating rapid conversion. Further in-situ Raman spectroscopy confirms the role of In bolstering the oxidized structure's stability within Bi2O3, critical for sustaining lattice oxygen during electrochemical CO2 reduction.

From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.

Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions. Molecular dynamics simulations confirmed that the fluspirilene-PDE5 complex is stable and maintains its structural integrity over time. Binding energy calculations further highlighted favorable interactions, indicating that the drug forms a strong and stable bond with PDE5. Additional analyses, including studies of protein dynamics and energy landscape mapping, revealed how the drug interacts dynamically with PDE5, adapting to different conformations and maintaining stability. These findings suggest that fluspirilene may modulate PDE5 activity, potentially offering therapeutic benefits for Alzheimer's disease. This study provides strong evidence for repurposing fluspirilene as a treatment for Alzheimer's and lays the foundation for further experimental and clinical investigations.

Probing the Redox Reactivity of Alkyl Bound Astatine: A Study on the Formation and Cleavage of a Stable At-C Bond.

The formation of a stable alkyl At-C bond occurs during the shipment of 211At on a 3-octanone-impregnated column and the reactivity of 211At stripped from columns has been studied. The 211At could not be recovered from the 3-octanone organic phase using nitric acid or sodium hydroxide, even up to 10 and 15.7 M, respectively. Several reducing and oxidizing agents, including hydrazine, hydroxylamine, ascorbic acid, ceric ammonium nitrate, potassium permanganate, sodium hypochlorite, and calcium hypochlorite were used to promote the recovery of 211At. The most effective reducing agent was hydroxylamine, where ∼70% of the 211At was recovered, while among oxidizing agents ceric ammonium nitrate, potassium permanganate, and sodium hypochlorite all showed near quantitative recovery of 211At. These results indicate an At-C bond is being formed during the shipment of the column and a redox reaction is required for bond cleavage to occur. DFT calculations have been used to propose several products of an AtO+-3-octanone reaction, with 4-astato-5-hydroxy-octa-3-one being the most probable.

Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations.

Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism. Extensive molecular dynamics (MD) simulations were performed for 12 μs to model free Cez2 and the diubiquitin (diUb) substrate-bound protein-protein complex in two different charge states of Cez2, each corresponding to a distinct reactive state in its catalytic cycle. The simulations were analyzed in terms of the relevant structural parameters for productive enzymatic catalysis. Reactive diUb-Cez2 complex configurations were identified, which lead to isopeptide bond cleavage and stabilization of the tetrahedral oxyanion intermediate. The reliability of these complexes was further assessed by quantum mechanics/molecular mechanics (QM/MM) optimizations. The results show that Cez2 follows a modified cysteine protease mechanism involving a catalytic Cys210/His367 dyad, with the oxyanion hole to be a part of the "C-loop," and polarization of His367 by the formation of a strictly conserved water bridge with Glu173. The third residue has a dual role in catalysis as it mediates substrate binding and polarization of the catalytic dyad. A similar mechanism was identified for Cezanne-1, the paralogue of Cez2. In general, our simulations provide valuable molecular information that may help in the rational design of selective inhibitors of Cez2 and closely related enzymes.

Isolated Neutral Organic Radical Unveiled Solvent-Radical Interaction in Highly Reducing Photocatalysis.

Diffusion-limited kinetics is a key mechanistic debate when consecutive photoelectron transfer (conPET) is discussed in photoredox catalysis. In situ generated organic photoactive radicals can access catalytic systems as reducing as alkaline metals that can activate remarkably stable bonds. However, in many cases, the extremely short-lived transient nature of these doublet state open-shell species has led to debatable mechanistic studies, hindering adoption and development. Herein, we document the use of an isolated and stable neutral organic nPrDMQA radical as a highly photoreducing species. The isolated radical offers a unique platform to investigate the mechanism behind the photocatalytic activity of organic photocatalyst radicals. The involvement of reduced solvent is observed, formed by single electron transfer (SET) between the short-lived excited state nPrDMQA radical and the solvent. In our detailed mechanistic studies, spectroscopic and chemical affirmation of solvent reduction is strongly evident. Reduction of aryl halides, including difluoroarenes is presented as a model study of the conPET method. Further, the activation of N2O, a greenhouse gas that is yet to be activated by photoredox catalysis, is showcased in the absence of a transition metal.

Synergistic linkage engineering in covalent organic frameworks for boosting photocatalytic hydrogen evolution

Enhancing π-conjugation and bond stability, along with the introduction of hydrophilic carboxyl groups into the COF channels, significantly boosts the photocatalytic performance, reusability, and durability of the COF.

Local structure and thermophysical properties of the molten salt FNaBe through ab initio molecular dynamics and experimental measurements

NaF-BeF2 molten salt has been proposed as one of the potential solvents and coolants for molten salt reactor due to its pertinent properties and satisfactory neutron capture cross-section. The experimental measurements combined theoretical simulations were employed to investigate comprehensive information on the structures and thermophysical properties of molten NaF-BeF2. Specifically, the specific heat capacity, density, and viscosity of NaF-BeF2 systems were determined using custom devices. Using the fitting relationships and simulations, the extrapolative data were also successfully obtained under the critical temperatures. The local structure including bond lengths, coordination structures and the potential of mean force, was further simulated by ab initio molecular dynamics in the temperature range of 673-1123 K. The coordination of Na and Be is predominantly characterized by six-fold and four-fold, respectively. Moreover, of Be-F bond is 7 times than Na-F bond, which suggests the stronger stability of Be-F bond in molten NaF-BeF2.

Formation of mono- and dual-labelled antibody fragment conjugates via reversible site-selective disulfide modification and proximity induced lysine reactivity.

Many protein bioconjugation strategies focus on the modification of lysine residues owing to the nucleophilicity of their amine side-chain, the generally high abundance of lysine residues on a protein's surface and the ability to form robustly stable amide-based bioconjugates. However, the plethora of solvent accessible lysine residues, which often have similar reactivity, is a key inherent issue when searching for regioselectivity and/or controlled loading of an entity. A relevant example is the modification of antibodies and/or antibody fragments, whose conjugates offer potential for a wide variety of applications. Thus, research in this area for the controlled loading of an entity via reaction with lysine residues is of high importance. In this article, we present an approach to achieve this by exploiting the quantitative and reversible site-selective modification of disulfides using pyridazinediones, which facilitates near-quantitative proximity-induced reactions with lysines to enable controlled loading of an entity. The strategy was appraised on several clinically relevant antibody fragments and enabled the formation of mono-labelled lysine-modified antibody fragment conjugates via the formation of stable amide bonds and the use of click chemistry for modular modification. Furthermore, through the use of multiple cycles of this novel strategy, an orthogonally bis-labelled lysine-modified antibody fragment conjugate was also furnished.

Exploring the effect of natural deep eutectic solvents on zein: Structural and functional properties.

This study evaluated the effects of chemical modification, including ethanol, acetic acid, and natural deep eutectic solvents (NADES), on the secondary and tertiary structures, hydrophobicity, free amine content, protein-protein interactions, and functional properties of zein. The NADES used included choline chloride: oxalic acid, choline chloride: urea, choline chloride: glycerol, and glucose: citric acid. The results reveal that the NADES system significantly altered zein's structures, as evidenced by Fourier transform infrared spectroscopy, fluorescence, and Ultraviolet-Visible Spectroscopy analysis. Circular dichroism spectroscopy analysis indicated significant conformational change in modified zein, with decreased α-helix and increased random coil content. Notably, the NADES system leads to greater disruption of hydrogen bonds and facilitates the exposure of hydrophobic regions compared to water, ethanol, and acetic acid systems. This resulted in enhanced solubility, surface hydrophobicity, and free amine content in zein, indicating a more significant change in protein structure. In contrast, water and acetic acid solvents maintained more stable disulfide bonds within zein, which correlates with lower solubility and less unfolding. The NADES system promoted interactions between zein and its solvent components, improving emulsifying properties. Water, ethanol, and acetic acid systems had higher solubility in urea, thiourea, and dithiothreitol than the NADES system, revealing disruption of both covalent and noncovalent bonds in zein modified by NADES. Overall, this study highlights the superior ability of the NADES system to modify zein's structure and functionality compared to conventional solvents, suggesting its potential for enhancing protein applications in the industrial production of foods.