Carboxylic Acid Groups Research Articles

Aqueous‐Phase Processing Affects the Formation and Size Distribution of Aerosol Organic Functional Groups During Heavy Pollution

AbstractSize‐resolved organic functional group (OFG) concentrations in aerosol particles were measured during January−February 2019 in Hefei, a major urban city in eastern China. Alkane, carboxylic acid, and hydroxyl groups were the main components of the organic aerosol (OA), contributing 35.0%, 22.5%, and 21.8%, respectively. The mass concentrations and size distributions of the OFGs strongly depended on ambient relative humidity (RH). Specifically, the OFG mass concentrations were 50% higher during the high‐RH periods than the low‐RH periods. The peak size of the OFGs size distribution was 0.56–1 μm during the high‐RH periods, while a peak size of 0.32–0.56 μm was observed during the low‐RH periods. In addition, the concentrations of the total OA, carboxylic acid, and hydroxyl groups were positively correlated with the photochemical age (PCA), with the high‐RH samples increasing faster (greater slope) with PCA and being associated with a higher oxygen‐to‐carbon ratio. These results suggest that aqueous‐phase processing likely enhanced the production of the OFGs, especially oxygenated functional groups. Further analysis of size distribution of the oxygenated OFGs and the viscosity of aerosols indicates that the secondary OFGs were formed via surface‐limited mechanisms under low‐RH conditions and volume‐limited mechanisms under high‐RH conditions. These findings reinforce the important role of multiphase chemistry in the formation and evolution of OAs.

Functionalization and performance of hybrid nanocellulose from plant-based/metal oxide nanocomposites for sustainable energy applications

Abstract Growing concerns over our dependence on finite, non-renewable resources like petroleum and metals have driven the development of eco-friendly technologies centered on advanced hybrid nanomaterials. Among these, the use of renewable nanocellulose – ranging in size from 1 to 100 nm – has gained significant attention in nanotechnology research. Derived from sustainable sources, nanocellulose offers notable advantages; however, challenges persist when integrating it with metal oxide nanoparticles (MONPs). These challenges include high reactivity in cellular environments, elevated production costs, and a tendency to aggregate, leading to instability in both liquid and dry states. Aggregation can impair uniform dispersion and result in sediment formation in certain applications. A promising solution to these challenges is hybridizing MONPs with functionalized nanocellulose, a method widely adopted by researchers. This approach is cost-effective, environmentally sustainable, and produces a renewable material with low density, excellent stability, superior mechanical properties, and biocompatibility. However, several questions remain unresolved, such as the most commonly used functionalization techniques for MONPs hybridization, the underlying mechanisms, and the specific benefits of this hybridization. Based on current findings, oxidation and carboxymethylation emerge as the most frequently used functionalization techniques for hybridizing MONPs with nanocellulose. These processes introduce carboxylic acid and carboxymethyl groups, respectively, which act as capping agents that readily bond with MONPs. This results in high degrees of substitution (DS) and improved nanoparticle dispersion. Furthermore, hybridization enhances properties such as thermal stability, UV protection, antibacterial activity, adsorption capacity, and mechanical performance, underscoring its potential for diverse applications.

Enhanced water resistance in post‐crosslinked polyurethane dispersion films using ethylene glycol diglycidyl ether

AbstractA post‐crosslinked polyurethane dispersion (PUD) with excellent water resistance was prepared using ethylene glycol diglycidyl ether (EGDGE) as a crosslinker. An anionic PUD was synthesized using dimethylol propionic acid as an internal emulsifier. During the curing process of the PUD film, the hydrophilic carboxylic acid and amine groups of PUD were consumed by the reaction with EGDGE. The reduction of hydrophilic functional groups and the increase of the crosslinking density effectively improved the water resistance of PUD films. In addition, the tensile strength of the PUD film increased from 54.2 MPa to a maximum of 75.3 MPa. The crosslinked structure reduced the crystallinity of the PUD film, which led to an increase in transparency.Highlights Novel EGDGE‐crosslinked PUD films with enhanced water resistance were developed. PUD samples introduced with EGDGE indicated favorable storage stability. Crosslinking reduced hydrophilic groups, improving thermal and mechanical stability. Optimized EGDGE content (6 wt%) yielded maximum tensile strength (75.3 MPa). Transparency increased due to suppressed phase separation in crosslinked PUDs.

Chemical profiling and characterisation of anthraquinone‐based polyphenols as biocolourants from Cortinarius semisanguineus

AbstractAnthraquinone dyes are known for their significant colour (brightness of shade in the red, blue and green areas) and light fastness properties compared with other synthetic dyes (such as azo‐based dyes). However, challenging multi‐step synthesis of anthraquinones and limited access to fewer substituents result in insufficient reactivity, hindering their wider industrial applications. Therefore, seeking highly substituted anthraquinone‐based colourants from natural sources is gaining interest among researchers. Notably, certain species of Dermocybe mushrooms are recognised for their red gills rich in anthraquinone colourants, which have been studied. However, limited knowledge of the chemotaxonomic characteristics of their species and molecular structure hinders wide use of their commercial applications. Our study screened extraction methods for their selectivity towards specific anthraquinone types, such as glycosidic vs non‐glycosidic, or those with carboxylic acid groups vs those without. In our observation, a sequential extraction strategy, starting with aqueous buffer extract followed by acetone extract, selectively yielded carboxylic acid‐containing anthraquinones and non‐carboxylic acid‐containing anthraquinones, respectively. We carried out a detailed analysis of anthraquinone‐based colourants in Cortinarius semisanguineus, comparing MS1‐MS2 profiles with two other species of the Dermocybe fungus group (Cortinarius sanguineus and Cortinarius ominosus), highlighting key interspecies differences in expressing certain anthraquinones or regioisomers. This study led to the structural identification of eleven natural anthraquinones and their glycosidic forms among these species. The carboxylic anthraquinones identified and characterised by their fragmentation pattern using MS1‐MS2 profiles include dermolutein, dermorubin, chlorodermorubin, endocrocin and chlorodermolutein, while the non‐carboxylic anthraquinones, primarily from the acetone extract, were dermoglaucin, emodin and dermocybin.

Syntheses and crystal structures of the cerium-based coordination polymers poly[(acetic acid)bis(μ-5-carboxythiophene-2-carboxylato)bis(μ-thiophene-2,5-dicarboxylato)dicerium(III)] and poly[(μ-acetato)aqua(μ4-thiophene-2,5-dicarboxylato)cerium(III)

The title compounds, [Ce2(C6H3SO4)2(C6H2SO4)2(CH3COOH)] n (1) and [Ce(CH3COO)(C6H2SO4)(H2O)] n (2) were synthesized by solvothermal reaction of Ce(NO3)3·6H2O with 2,5-thiophenedicarboxylic acid (H2TDC, C6H4SO4) and acetic acid in acetonitrile or ethanol/water, respectively. These compounds were obtained as single crystals among other crystalline phases. Both compounds belong to the family of three-dimensional coordination polymers. The asymmetric unit of 1 consists of two CeIII cations, two TDC2− dianions, two HTDC− anions and one acetic acid ligand, all of them located in general positions. The two CeIII cations are each coordinated by eight oxygen atoms in the form of distorted square antiprisms. These are bridged by carboxylate and carboxylic acid groups, forming mono-periodic hybrid inorganic building units (IBUs), which are connected into a three-dimensional network by the TDC2− and HTDC− ligands. Compound 2 has an asymmetric unit composed of one CeIII cation, one TDC2− dianion, one acetate anion and one water molecule in general positions. The cerium atom is eightfold coordinated by oxygen atoms. Edge-sharing CeO8 polyhedra form a dinuclear IBU (Ce2O14). This IBU is bridged by six TDC2− linkers to nine other IBUs, forming a three-dimensional framework. Both title compounds exhibit additional O—H...O hydrogen bonds. Powder X-ray diffraction shows that both compounds were not obtained as pure phases.

2,4-Dichlorophenoxyacetic Acid in the Gas and Crystal Phases and Its Intercalation in Montmorillonite-An Experimental and Theoretical Study.

Many properties of 2,4-dichlorophenoxyacetic acid (2,4-D) depend on its molecular environment, such as whether it is an isolated molecule, a dimer, or in a crystalline state. The molecular geometry, conformational analysis, and vibrational spectrum of 2,4-D were theoretically calculated using Density Functional Theory (DFT) methods. A new slightly more stable conformer was found, which is different to those previously reported. The most stable conformer shows a dimer by means of hydrogen bonds between the carboxylic groups of both molecules, which agrees with the experimental results. The crystal structure of 2,4-D was also calculated with 3D periodical boundary conditions at the DFT level. From the theoretical IR spectra, a vibrational analysis of this molecular species was accomplished, and the bands were reassigned. 1H and 13C NMR in the dissolution and solid states, respectively, showed intramolecular hydrogen bonds between carboxylic acid groups. The dimer is more stable than the isolated molecule. All these results indicated that the dimer can also exist in the solid state, which could explain the low solubility of this compound. In addition, the intercalation of 2,4-D into the confined interlayer space of montmorillonite was also calculated, and it was found that the adsorption is energetically favourable. This result was experimentally confirmed. These findings predicted that these natural clay minerals, which are found in the environment, can be excellent adsorbents for the 2,4-D pollutant.

Highly electroactive thiazolium [5,4-d]thiazol-2,5-dicarboxylicacid-silver electrochemiluminescent metal-organic frameworks: synthesis, properties and application in glutathione detection.

Thiazolo[5,4-d]thiazole-2,5-dicarboxylic acid (H2Thz), a thiazolothiazole (TTz) derivative with carboxylic acid groups, was synthesized as a ligand for the creation of five MOFs, each associated with distinct metal ions including Ag+, Mn2+, Co2+, Zn2+, and Cu2+. The cathodic electrochemiluminescence (ECL) of H2Thz and the resulting MOFs was investigated. H2Thz was found to generate ECL signals, but this process was heavily reliant on potassium persulfate (K2S2O8) as a co-reactant. However, the Ag-MOF, formed with H2Thz as the ligand, exhibited substantial ECL signals without the need for any co-reactant, which is different from other metal-containing MOFs. The smaller band gap, higher electron mobility and the unique electrocatalytic activity of Ag+ ions were confirmed to be the reasons for the excellent ECL performance of Ag-MOF. The interaction between thiol group of glutathione (GSH) and Ag-MOF suppressed the ECL signal of the Ag-MOF-K2S2O8 system. Based on this, a sensitive ECL method for GSH was developed and effectively utilized for GSH quantification in cell lysates.

Roadmap for Designing Donor-π-Acceptor Fluorophores in UV-Vis and NIR Regions: Synthesis, Optical Properties and Applications.

Donor acceptor (D-π-A) fluorophores containing a donor unit and an acceptor moiety at each end connected by a conjugated linker gained attention in the last decade due to their conjugated system and ease of tunability. These features make them good candidates for various applications such as bioimaging, photovoltaic devices and nonlinear optical materials. Upon excitation of the D-π-A fluorophore, intramolecular charge transfer (ICT) occurs, and it polarizes the molecule resulting in the 'push-pull' system. The emission wavelengths of fluorophores can be altered from UV-vis to NIR region by modifying the donor unit, acceptor moiety and the π linker between them. The NIR emitting fluorophores with restricted molecular rotations are used in aggregation-induced emission (AIE). D-π-A fluorophores with carboxylic acid and cyano groups are preferred in photovoltaic applications, and fluorophores with large surface area are used for two photon absorbing applications. Herein, we report the synthesis, optical properties, and applications of various D-π-A fluorophores in UV-vis and NIR region.

Preparation, Evaluation, In vitro Anti-diabetic and Stability Studies of Glibenclamide Loaded Cocrystals

Background: Glibenclamide (BCS Class–II .Drug) has poor solubility and high permeability. In the co-crystallization technique, drugs are combined with a suitable coformer via Hbonding. Glibenclamide cocrystals have been prepared with various coformers but glibenclamide cocrystals with vanillic acid have not been prepared yet. Objective: To prepare glibenclamide cocrystals with vanillic acid coformer and evaluate them using various techniques, along with in vivo antidiabetic studies and stability studies. Method: Cocrystals containing glibenclamide were produced with vanillic acid coformer by the solvent evaporation method in a 1:1 molar ratio. Result: In FTIR analysis, an H-bond is formed between the amide group of the drug and the carboxylic acid group of the coformer. With the help of DSC and HSM, the melting point of cocrystals was observed at a different point compared to the melting point of glibenclamide drug and vanillic acid coformer. In the XRD analysis of cocrystals, peaks with high intensity were observed at different points than that of the drug and coformer, confirming the crystalline nature of the formulation. During in vitro dissolution studies, cocrystals showed a better dissolution profile compared to the marketed formulation and the pure drug in both acidic and alkaline media. In vivo anti- diabetic studies were conducted using male Wistar rats, confirming that the glucose reduction percentage from cocrystals was more than that of the pure drug. During stability studies, no significant changes occurred in the dissolution profile of the formulation, which indicated that the formulation was stable after storage at an ambient temperature. Conclusion: The results obtained from various characterization techniques indicate that glibenclamide cocrystals formed from vanillic acid enhance the solubility of glibenclamide.

Ring-Opening Polymerization of Surface Ligands Enables Versatile Optical Patterning and Form Factor Flexibility in Quantum Dot Assemblies.

The evolution of display technologies is rapidly transitioning from traditional screens to advanced augmented reality (AR)/virtual reality (VR) and wearable devices, where quantum dots (QDs) serve as crucial pure-color emitters. While solution processing efficiently forms QD solids, challenges emerge in subsequent stages, such as layer deposition, etching, and solvent immersion. These issues become especially pronounced when developing diverse form factors, necessitating innovative patterning methods that are both reversible and sustainable. Herein, a novel approach utilizing lipoic acid (LA) as a ligand is presented, featuring a carboxylic acid group for QD surface attachment and a reversible disulfide ring structure. Upon i-line UV exposure, the LA ligand initiates ring-opening polymerization (ROP), crosslinking the QDs and enhances their solvent resistance. This method enables precise full-color QD patterns with feature sizes as small as 3µm and pixel densities exceeding 3788 ppi. Additionally, it supports the fabrication of stretchable QD composites using LA-derived monomers. The reversible ROP process allows for flexibility, self-healing, and QD recovery, promoting sustainability and expanding QD applications for ultra-fine patterning and on-silicon displays.

PIII/PV═O Redox Catalysis Mediated Thioesterification of Carboxylic Acids with Disulfides under Air Conditions.

An efficient organophosphorus-catalyzed thiocarbonylation reaction of disulfides with carboxylic acids under air conditions was described. Various functional groups on carboxylic acids and disulfides can be tolerated under the present reaction conditions, affording thioesters in good to excellent yields. This method exhibited excellent chemoselectivity and can be applied for the late-stage functionalization of drug molecules containing a carboxylic acid group.

Molecular Design of Hole-Collecting Materials for Co-Deposition Processed Perovskite Solar Cells: A Tripodal Triazatruxene Derivative with Carboxylic Acid Groups.

High-performance and cost-effective hole-collecting materials (HCMs) are indispensable for commercially viable perovskite solar cells (PSCs). Here, we report an anchorable HCM composed of a triazatruxene core connected with three alkyl carboxylic acid groups (3CATAT-C3). In contrast to the phosphonic acid-containing tripodal analog (3PATAT-C3), 3CATAT-C3 molecules can form a hydrophilic monolayer on a transparent conducting oxide surface, which is beneficial for subsequent perovskite film deposition in the traditional layer-by-layer fabrication process. More importantly, the larger diffusion coefficient and higher surface energy make 3CATAT-C3 suitable for the simplified, cost-effective one-step co-deposition process in which 3CATAT-C3 was directly added as part of the perovskite precursor solution. 3CATAT-C3 is predominantly located at the perovskite bottom surface after spin-coating the mixed precursor solution, facilitating charge extraction. Devices with 3CATAT-C3 fabricated by this co-deposition method exhibit superior performance with a champion power conversion efficiency of over 23%. The unencapsulated devices showed good operational stability (retaining 90% of the initial output after 100 h), thermal durability (retaining 95% of the initial value after heating at 105 °C under air), and excellent storage stability (showing no drop in performance over 8000 h). Based on the results of time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) and diffusion order nuclear magnetic resonance spectroscopy (DOSY), we elucidated the effect of anchoring groups on the performance of the tripodal HCMs in PSCs as well as the mechanism of the co-deposition fabrication process. Our findings provide valuable insights for the molecular design of multifunctional hole-collecting materials, further advancing the performance of perovskite solar cells.

From Infection to Tumor: Exploring the Therapeutic Potential of Ciprofloxacin Derivatives as Anticancer Agents.

Ciprofloxacin, a widely used second-generation fluoroquinolone for treating bacterial infections, has recently shown notable anticancer properties. This review explores progress in developing ciprofloxacin derivatives with anticancer properties, emphasizing key structural changes that improve their therapeutic effectiveness by modifying the basic group at position 7, the carboxylic acid group at position 3, or both. It further investigates the mechanisms by which these derivatives fight cancer, such as inducing apoptosis, arresting the cell cycle, inhibiting topoisomerase I and II, preventing tubulin polymerization, suppressing interleukin 6, blocking thymidine phosphorylase, inhibiting multidrug resistance proteins, and hindering angiogenesis. Additionally, it outlines their future directions, such as enhancing their efficacy, selectivity, and investigating potential synergy with other chemotherapeutic agents, offering a promising avenue for developing new therapies for cancer.

Tin(IV)Porphyrin-Based Porous Coordination Polymers as Efficient Visible Light Photocatalyst for Wastewater Remediation.

Two porphyrin-based polymeric frameworks, SnP-BTC and SnP-BTB, as visible light photocatalysts for wastewater remediation were prepared by the solvothermal reaction of trans-dihydroxo-[5,15,10,20-tetrakis(phenyl)porphyrinato]tin(IV) (SnP) with 1,3,5-benzenetricarboxylic acid (H3BTC) and 1,3,5-tris(4-carboxyphenyl)benzene (H3BTB), respectively. The strong bond between the carboxylic acid group of H3BTC and H3BTB with the axial hydroxyl moiety of SnP leads to the formation of highly stable polymeric architectures. Incorporating the carboxylic acid group onto the surface of SnP changes the conformational frameworks as well as produces rigid structural transformation that includes permanent porosity, good thermodynamic stability, interesting morphology, and excellent photocatalytic degradation activity against AM dye and TC antibiotic under visible light irradiation. The photocatalytic degradation activities of AM dye were found to be 95% by SnP-BTB and 87% by SnP-BTC within 80 min. Within 60 min of visible light exposure, the photocatalytic degradation activities of TC antibiotic were found to be 70% by SnP-BTB and 60% by SnP-BTC. The enhanced catalytic photodegradation performances of SnP-BTB and SnP-BTC were attributed to the synergistic effect between SnP and carboxylic acid groups. The carboxylic acid connectors strongly resist the separation of SnP from the surface of SnP-BTB and SnP-BTC during the photodegradation experiments. Therefore, the high degradation rate and low catalyst loading make SnP-BTB or SnP-BTC more efficient than other reported catalysts. Thus, the present investigations on the porphyrin-based photocatalysts hold great promise in tackling the treatment of dyeing wastewater.

An elastic siderophore synthetase and rubbery substrates assemble multimeric linear and macrocyclic hydroxamic acid metal chelators.

The trihydroxamic acid bacterial siderophore desferrioxamine B (DFOB, 1) produced by the DesABCD biosynthetic cluster coordinates metals beyond Fe(iii), which identifies potential to modify this chelator type to broaden metal sequestration and/or delivery applications. Rather than producing discrete chelators by total chemical synthesis from native monomers including N-hydroxy-N-succinyl-cadaverine (HSC, 2), the recombinant siderophore synthetase from Salinispora tropica CNB-440 (StDesD) was used with different substrate combinations to produce biocombinatorial mixtures of hydroxamic acid chelators. The mixtures were screened with Ga(iii) or Zr(iv) as surrogates of immunological positron emission tomography (PET) imaging radiometals 68Ga(iii) or 89Zr(iv) to inform known or new coordination chemistry. The last-in-line enzyme DesD forms amide bonds between two equivalents of 2 and N-hydroxy-N-acetyl-cadaverine to produce trimeric 1. Although hexadentate 1 is the terminal product evolved for Fe(iii) complexation, it was conceived amine-containing 1 might remain a viable DesD substrate for further iteration with 2 to generate higher-order hydroxamic acid multimers. Incubation of StDesD, cofactors ATP and Mg(ii), and 1 and 2, generated the octadentate hydroxamic acid DFOB-HSC (3) (previously characterised and named DFO*), decadentate DFOB-(HSC)2 (4), dodecadentate DFOB-(HSC)3 (5) and tetradecadentate DFOB-(HSC)4 (6). The system with StDesD and 2 alone generated a set of linear multimers containing flanking amine and carboxylic acid groups (HSC) x -L (x = 2 (7), x = 3 (8), x = 4 (9), x = 5 (10)) and a subset of the cognate ring-closed macrocycles (HSC) x -MC (x = 3 (12), x = 4 (13), x = 5 (14), with x = 2 (11) not detected). Liquid chromatography-mass spectrometry metal screening experiments detected 1 : 1 complexes of Ga(iii) or Zr(iv) and 1, 3-5, 8-10, and 12-14. Complexes of 2 : 1 stoichiometry were formed between Ga(iii) and the high-denticity, high-cavity-volume chelators 4-6, and 14. A processive intra-cavity assembly mechanism has been posited for this flexible siderophore synthetase in delivering a large set of multimeric chelators.

1,4,5-Trisubstituted-carboxylated 1,2,3-triazoles: an unconventional class of ribonuclease A inhibitors.

The "catalytic triad" present at the active site of ribonuclease A (RNase A) is responsible for the cleavage of the 5'-phosphodiester bond; amino acid residues His12, Lys41 and His119 constituting this triad provide a positively charged environment at the physiological pH. Based on docking studies, 1,4,5-trisubstituted-carboxylated 1,2,3-triazoles (1,4,5-TTs) were identified as a new class of RNase A inhibitors. Therefore, two different groups of 1,4,5-TTs, functionalized with carboxylic acid groups, were synthesized by reacting pre functionalized butyne-1,4-diol derivatives with several aryl/alkyl azides under solvent and catalyst free conditions. Inhibitory properties of the new molecules with heteroatom linked carboxylic acid "CH2XCH2CO2H" (X = S, O) functionalities were investigated by performing qualitative and quantitative biophysical studies. All the "CH2S" and "CH2O" linked acid derivatives (6a-e, 6f'-g' and 6h, and 8a-e, 8f'-g' and 8h) exhibited significant competitive inhibition with inhibition constant values (Ki) ranging from 9 to 34 μM determined by steady state enzyme kinetics. Uracil based bisthioglycolic acid (6h) and carboxylic acid based bisoxyacetic acid (8g') derivatives were found to be the most promising inhibitors with Ki values of 9.9 ± 0.7 and 15.6 ± 0.6 μM, respectively. Additional molecular docking studies revealed that a sufficient number of hydrogen bonding interactions were generated from various functional groups of inhibitors and the amino acid residues present at important subsites of RNase A. The study also established that the free rotating "CH2X" arms of 1,4,5-TTs provided a unique shape to accommodate the molecule within the active site cleft. A fairly good idea about the structure activity relationship (SAR) was obtained by correlating experimentally determined Ki values and the corresponding docking poses. This study reports an unconventional class of non-sugar, non-nucleosidic 1,4,5-TT based competitive inhibitors of RNase A.

Polycyclic aromatic polymer nanoparticles show potent infectious particle adsorption capability.

Nonspecific viral adsorption by polymer nanoparticles is more economical and superior in terms of operating cost and energy efficiency than viral adsorption using virus-specific antibodies and filtration techniques involving size exclusion in the order of tens of nanometres. In this study, we synthesised four types of polycyclic aromatic polymer (ArP) nanoparticles with different structures and evaluated their virus adsorption capability for infectious particles of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ArP nanoparticles with a diameter of approximately 500 nm were prepared by one-pot precipitation polymerisation using structural isomers of bifunctional dihydroxynaphthalene (1,5-dihydroxynaphthalene and 2,6-dihydroxynaphthalene) as phenol monomers, as well as 3-hydroxybenzoic acid and 3-aminophenol as comonomers to introduce carboxylic acid and amino groups, respectively. This wide range of phenolic monomers offers a powerful molecular design capability, enabling the optimisation of surface properties for the adsorption of various infectious virus particles. The virus adsorption capacity of the ArP nanoparticles exceeded 20 000 plaque-forming units and was found to be correlated with the nitrogen (primary and secondary amines) and quinone contents on the ArP nanoparticle surface. Furthermore, a polyvinylidene difluoride membrane filter uniformly coated with the ArP nanoparticles could remove viruses by filtration in a flow system.

Hemocompatible nucleosome-inspired heparin-mimicking hydrogel microspheres for safe and efficient extracorporeal removal of circulating histones in critically ill patients.

Circulating histones have been identified as essential mediators that lead to hyperinflammation, platelet aggregation, coagulation cascade activation, endothelial cell injury, multiple organ dysfunction, and death in severe patients with sepsis, multiple trauma, COVID-19, acute liver failure, and pancreatitis. Clinical evidence suggests that plasma levels of circulating histones are positively associated with disease severity and survival in patients with such critical diseases. However, safe and efficient therapeutic strategies targeting circulating histones are lacking in current clinical practice. Extracorporeal blood purification, a widely used life support technique in intensive care units, is a promising therapeutic option for eliminating circulating histones. Inspired by electrostatic interactions between DNA chains and histones in natural nucleosomes, we propose a "one stone kills two birds" strategy to combat histone-related critical diseases by developing heparin-mimicking hydrogel microspheres (RCHMs). On one hand, the heparin-mimicking hydrogel structure inside RCHMs contains a large number of carboxyl and sulphonic acid groups by in situ cross-linking polymerization, which endows the RCHMs with excellent hemocompatibility. On the other hand, the RCHMs can adsorb circulating histones through electrostatic interactions. Our results demonstrate that the RCHMs do not cause significant hemolysis, blood cell activation and complement activation, with improved anti-protein contamination properties. The tailored RCHM microspheres (A3M1) can efficiently and selectively adsorb 91.16% of calf thymus histones with an adsorption capacity of 20.47 μg mg-1 within 4 h. Moreover, the RCHMs significantly attenuate histone-mediated thrombocytopenia, platelet aggregation, and endothelial cell death. Therefore, the RCHMs are promising hemoperfusion adsorbents for extracorporeal removal of circulating histones from the blood of critically ill patients, providing a new insight into the management of multiple histone-related disorders.

Discovery of potent and selective factor XIa inhibitors incorporating triazole-based benzoic acid as novel P2' fragments: Molecular dynamics simulations and anticoagulant activity.

Factor XIa (FXIa) has emerged as a novel anticoagulant target with a reduced risk of bleeding. However, due to the nearly identical residues it shares with its closest homologue, plasma kallikrein (PKa), only a few selective FXIa inhibitors have been reported. Herein, we describe the discovery of novel triazole-based pyridone derivatives as potent and selective FXIa inhibitors. Structural optimization identified triazole-based benzoic acids as optimal P2' fragments. The representative compound (S)-10h (IC50=0.38nM for FXIa) was approximately 3-fold more potent than asundexian for FXIa, along with up to 150-fold selectivity over PKa (13-fold for asundexian) and up to 100,000-fold selectivity over FXa and thrombin (5000-fold for asundexian). Extensive molecular dynamics simulations and free energy calculations revealed that electrostatic interactions with varied residues near the binding site, particularly the loop at the bottom of the S2' pocket (IP-loop), are critical factors contributing to the improved selectivity over PKa. Calculations of electrostatic potential (ESP) surfaces illustrated that FXIa forms a more positive ESP than PKa, thrombin, and FXa, which attracts the carboxylic acid group of the designed compounds, enhancing both potency and selectivity. Moreover, compound (S)-10h demonstrated potent in vitro anticoagulant activity with an EC1.5X value of 0.55μM for aPTT, without interfering with PT up to 100μM. Thus, compound (S)-10h represents a promising lead for further optimization as a novel anticoagulant agent.

Optoelectronic Properties and Fluorescence Lifetime Imaging Application of Donor-Acceptor Dyads Derived From 2,6-DicarboxyBODIPY.

Donor-acceptor BODIPY dyads, functionalized at the 2 and 6 positions with benzyl ester (BDP-DE) or carboxylic acid (BDP-DA) groups, were synthesized and characterized for their optoelectronic properties. The introduction of carbonyl groups increased the reduction potential of the BODIPY core by 0.15-0.4 eV compared to alkyl-substituted analogs. These dyads exhibited efficient intramolecular charge separation and triplet state formation through spin-orbit charge transfer intersystem crossing (SOCT-ISC), achieving singlet oxygen quantum yields of up to 92%, modulated by solvent polarity. The fluorescence and singlet oxygen generation of BDP-DAs depended on the ionization state of the carboxylic groups. Complexation of BDP-DAs with bovine serum albumin (BSA) significantly extended their excited state lifetimes, as shown by time-resolved fluorescence measurements. Fluorescence lifetime imaging microscopy (FLIM) studies in human colorectal carcinoma (HCT116) cells and pig small intestinal organoids (enteroids) revealed subcellular localization patterns. Specifically, the diacid with a dimethoxyphenyl group (DA1) displayed longer lifetimes in lipid-droplet-like structures, while the diacid containing a meso-anthracenyl group (DA2) formed distinct 'islands' in cell monolayers, exhibiting a lifetime gradient. These results underscore the potential of donor-acceptor BODIPYs as fluorescent probes for distinguishing cellular environments.