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1.
J Environ Sci (China) ; 147: 714-725, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003084

RESUMO

In this study, an efficient stabilizer material for cadmium (Cd2+) treatment was successfully prepared by simply co-milling olivine with magnesite. Several analytical methods including XRD, TEM, SEM and FTIR, combined with theoretical calculations (DFT), were used to investigate mechanochemical interfacial reaction between two minerals, and the reaction mechanism of Cd removal, with ion exchange between Cd2+ and Mg2+ as the main pathway. A fixation capacity of Cd2+ as high as 270.61 mg/g, much higher than that of the pristine minerals and even the individual/physical mixture of milled olivine and magnesite, has been obtained at optimized conditions, with a neutral pH value of the solution after treatment to allow its direct discharge. The as-proposed Mg-based stabilizer with various advantages such as cost benefits, green feature etc., will boosts the utilization efficiency of natural minerals over the elaborately prepared adsorbents.


Assuntos
Cádmio , Compostos de Ferro , Compostos de Magnésio , Silicatos , Poluentes Químicos da Água , Cádmio/química , Poluentes Químicos da Água/química , Compostos de Magnésio/química , Silicatos/química , Compostos de Ferro/química , Adsorção , Modelos Químicos , Purificação da Água/métodos
2.
Adv Sci (Weinh) ; : e2404071, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958542

RESUMO

α-halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon-boron and carbon-halogen bonds into a broad range of carbon-X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst-free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α-halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals.

3.
Cell Rep ; 43(7): 114513, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003736

RESUMO

Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

4.
Methods Enzymol ; 701: 387-424, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39025577

RESUMO

The Helfrich free energy is widely used to model the generation of membrane curvature due to different physical and chemical components. The governing equations resulting from the energy minimization procedure are a system of coupled higher order partial differential equations. Simulations of membrane deformation for obtaining quantitative comparisons against experimental observations require computational schemes that will allow us to solve these equations without restrictions to axisymmetric coordinates. Here, we describe one such tool that we developed in our group based on discrete differential geometry to solve these equations along with examples.


Assuntos
Proteínas de Membrana , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Membrana Celular/metabolismo , Membrana Celular/química , Modelos Biológicos , Termodinâmica , Simulação por Computador , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo
5.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998228

RESUMO

The 1:1 resveratrol-piperazine cocrystal was successfully synthesized and scaled-up to 300 g scale with the mechanochemical method, as a result of investigating key process parameters, namely the solvent and the grinding time. The use of water, ethanol or ethanol-water mixtures and reaction times up to 50 min were evaluated relative to the dry grinding process. Cocrystal formation and purity were monitored through X-ray diffraction and calorimetry measurements. The dry grinding resulted in an incomplete cocrystal formation, while the use of water or water-ethanol mixture yielded a monohydrate solid phase. Pure ethanol was found to be the optimal solvent for large-scale cocrystallization, as it delivered cocrystals with high crystallinity and purity after 10-30 min grinding time at the laboratory scale. Notably, a relatively fast reaction time (30-60 min) was sufficient for the completion of cocrystallization at larger scales, using a planetary ball mill and a plant reactor. Also, the obtained cocrystal increases the aqueous solubility of resveratrol by 6%-16% at pH = 6.8. Overall, this study highlights the potential of solvent-assisted mechanochemical synthesis as a promising new approach for the efficient production of pure resveratrol-piperazine cocrystals.

6.
Materials (Basel) ; 17(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38998390

RESUMO

This paper focuses on high-entropy spinels, which represent a rapidly growing group of materials with physicochemical properties that make them suitable for hydrogen energy applications. The influence of high-pressure pure hydrogen on the chemical stability of three high-entropy oxide (HEO) sinter samples with a spinel structure was investigated. Multicomponent HEO samples were obtained via mechanochemical synthesis (MS) combined with high-temperature thermal treatment. Performing the free sintering procedure on powders after MS at 1000 °C for 3 h in air enabled achieving single-phase (Cr0.2Fe0.2Mg0.2Mn0.2Ni0.2)3O4 and (Cu0.2Fe0.2Mg0.2Ni0.2Ti0.2)3O4 powders with a spinel structure, and in the case of (Cu0.2Fe0.2Mg0.2Ti0.2Zn0.2)3O4, a spinel phase in the amount of 95 wt.% was achieved. A decrease in spinel phase crystallite size and an increase in lattice strains were established in the synthesized spinel powders. The hydrogenation of the synthesized samples in a high-pressure hydrogen atmosphere was investigated using Sievert's technique. The results of XRD, SEM, and EDS investigations clearly showed that pure hydrogen at temperatures of up to 250 °C and a pressure of up to 40 bar did not significantly impact the structure and microstructure of the (Cr0.2Fe0.2Mg0.2Mn0.2Ni0.2)3O4 ceramic, which demonstrates its potential for application in hydrogen technologies.

7.
Small ; : e2404283, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016994

RESUMO

Efficient sodium ion storage in graphite is as yet unattainable, because of the thermodynamic instability of sodium ion intercalates-graphite compounds. In this work, sodium fluorozirconate (Na3ZrF7, SFZ) functionalized graphite (SFZ-G) is designed and prepared by the in situ mechanochemical silicon (Si) replacement of sodium fluorosilicate (Na2SiF6, SFS) and functionalization of graphite at the same time. During the mechanochemical process, the atomic Si in SFS is directly replaced by atomic zirconium (Zr) from the zirconium oxide (ZrO2) balls and container in the presence of graphite, forming SFZ-G. The resulting SFZ-G, working as an anode material for sodium ion storage, shows a significantly enhanced capacity of 418.7 mAh g-1 at 0.1 C-rate, compared to pristine graphite (35 mAh g-1) and simply ball-milled graphite (BM-G, 200 mAh g-1). In addition, the SFZ-G exhibits stable sodium-ion storage performance with 86% of its initial capacity retention after 1000 cycles at 2.0 C-rate.

8.
Materials (Basel) ; 17(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930375

RESUMO

Chitosan is a promising adsorbent for removing a wide range of pollutants from wastewater. However, its practical application is hindered by instability in acidic environments, which significantly impairs its adsorption capacity and limits its utilization in water purification. While cross-linking can enhance the acid stability of chitosan, current solvent-based methods are often costly and environmentally unfriendly. In this study, a solvent-free mechanochemical process was developed using high-energy ball milling to cross-link chitosan with various polyanionic linkers, including dextran sulfate (DS), poly[4-styrenesulfonic acid-co-maleic acid] (PSSM), and tripolyphosphate (TPP). The mechanochemically cross-linked (MCCL) chitosan products exhibited superior adsorption capacity and stability in acidic solutions compared to pristine chitosan. Chitosan cross-linked with DS (Cht-DS) showed the highest Reactive Red 2 (RR2) adsorption capacity, reaching 1559 mg·g-1 at pH 3, followed by Cht-PSSM (1352 mg·g-1) and Cht-TPP (1074 mg·g-1). The stability of MCCL chitosan was visually confirmed by the negligible mass loss of Cht-DS and Cht-PSSM tablets in pH 3 solution, unlike the complete dissolution of the pristine chitosan tablet. The MCCL significantly increased the microhardness of chitosan, with the order Cht-DS > Cht-PSSM > Cht-TPP, consistent with the RR2 adsorption capacity. When tested on simulated rinsing wastewater from chromium electroplating, Cht-DS effectively removed Cr(VI) (98.75% removal) and three per- and polyfluoroalkyl substances (87.40-95.87% removal), following pseudo-second-order adsorption kinetics. This study demonstrates the potential of the cost-effective and scalable MCCL approach to produce chitosan-based adsorbents with enhanced stability, mechanical strength, and adsorption performance for treating highly acidic industrial wastewater containing a mixture of toxic pollutants.

9.
Polymers (Basel) ; 16(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38931982

RESUMO

Recycling flexible polyurethane foam (F-PUF) scraps is difficult due to the material's high cross-linking structure. In this work, a wedge-block-reinforced extruder with a considerable enhanced shear extrusion and stretching area between the rotating screw and the stationary wedge blocks was utilized to recycle F-PUF scraps into powder containing surface-active hydroxyl groups. The powder was then utilized for the quantitative replacement of polyol in the foaming process. Characterizations showed that the continuous shear extrusion and stretching during the extrusion process reduced the volume mean diameter (VMD) of the F-PUF powder obtained by extruding it three times at room temperature to reach 54 µm. The -OH number (OHN) of the powder prepared by extruding it three times reached 19.51 mgKOH/g due to the mechanochemical effect of the powdering method. The F-PUF containing recycled powder used to quantitively replace 10 wt.% polyol was similar in microstructure and chemical structure to the original F-PUF, with a compression set of 2%, indentation load deflection of 21.3 lbf, resilience of 43.4%, air permeability of 815.7 L/m2·s, tensile strength of 73.0 Kpa, and tear strength of 2.3 N/cm, indicating that the recycling method has potential for industrial applications.

10.
J Environ Manage ; 363: 121254, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850909

RESUMO

Despite being composed of recyclable materials, the main technological challenge of multilayer carton packs involves the efficient decompatibilization of the cellulosic, polymeric, and metallic phases. Here, a simple two-step mechanochemical process is described that uses only aqueous media and mechanical force to promote phase separation in order to fully recycle multi-layer carton packaging. The first step produces value-added micro- and nanocellulose, while in the second step, aluminum is extracted, forming precipitated aluminum and aluminum oxyhydroxides. Solid polyethylene (PE) remains with a degree of purity defined by the process efficiency. The results show that cellulose is efficiently extracted and converted into micro- and nanocellulose after 15 min of milling. In the second stage, approximately 90% of the aluminum is extracted from the PE after 15 min of milling. Due to the separation and drying medium conditions, the finely divided particles of extracted aluminum also have oxyhydroxides in their composition. It is believed that a passivation layer forms on the metallic aluminum particle. The techno-economic analysis revealed a positive net present value (NPV) of $17.5 million, with a minimum selling price of 1.62 USD/kg of cellulose. The environmental analysis concluded that most of the environmental impact of the process is associated with the entry of carton packages into the system, incorporating a small environmental load related to the industrial process. The results indicate a promising option toward a circular economy and carbon neutrality.


Assuntos
Celulose , Reciclagem , Celulose/química , Alumínio/química , Polietileno/química
11.
Sci Total Environ ; 946: 174117, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38908592

RESUMO

Mechanochemical techniques have been garnering growing attention in remediation of contaminated soil. This paper summarizes the performance, mechanism, influential factors, and environmental impacts of mechanochemical remediation (MCR) for persistent organic pollutants (POPs) contaminated soil and heavy metal(loid) s (HMs) contaminated soil. Firstly, in contrast to other technologies, MCR can achieve desirable treatment of POPs, HMs, and co-contaminated soil, especially with high-concentration pollutants. Secondly, POPs undergo mineralization via interaction with mechanically activated substances, where aromatic and aliphatic pollutants in soil may go through varied degradation routes; inorganic pollutants can be firmly combined with soil particles by fragmentation and agglomeration induced by mechanical power, during which additives may enhance the combination but their contact with anionic metal(loid)s may be partially suppressed. Thirdly, the effect of MCR primarily hinges on types of milling systems, the accumulation of mechanical energy, and the use of reagents, which is basically regulated through operating parameters: rotation speed, ball-to-powder ratio, reagent-to-soil ratio, milling time, and soil treatment capacity; minerals like clay, metal oxides, and sand in soil itself are feasible reagents for remediation, and alien additives play a crucial role in synergist and detoxification; additionally, various physicochemical properties of soil might influence the mechanochemical effect to varying degrees, yet the key influential performance and mechanism remain unclear and require further investigation. Concerning the assessment of soil after treatment, attention needs to be paid to soil properties, toxicity of POPs' intermediates and leaching HMs, and long-term appraisement, particularly with the introduction of aggressive additives into the system. Finally, proposals for current issues and forthcoming advancements in this domain are enumerated in items. This review provides valuable insight into mechanochemical approaches for performing more effective and eco-friendly remediation on contaminated soil.

12.
Sci Total Environ ; 946: 174073, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38909802

RESUMO

Superhydrophobic porous organic polymers are potential sorbents for volatile organic compounds (VOCs) pollution control by suppressing the competition of water molecules on their surfaces. However, the synthesis of superhydrophobic reagents usually requires large amounts of organic solvents and a long reaction time (≥ 24 h). Herein, a green mechanochemical method was developed to synthesize a superhydrophobic polymer (MSHMP-1) with the advantages of using a small amount of organic solvents (5 mL/g) and a short reaction time (2 h). Meanwhile, MSHMP-1 with a water contact angle (WCA) of 162° exhibited a dramatically rich pore structure as revealed by its specific surface area (SSA) of 1780 m2/g. The decrease in the adsorption of benzene on MSHMP-1 due to the competition of water molecules, even at relative humidity of 90 %, was nonsignificant (<10 %), indicating the great application potential of MSHMP-1 in hydrophobic adsorption. Moreover, the adsorption capacity of MSHMP-1 was maintained after at least five adsorption-desorption cycles. Therefore, MSHMP-1 can be a remarkable adsorbent for the removal of hazardous VOCs, especially at high humidity levels.

13.
Sci Total Environ ; 946: 174154, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38942310

RESUMO

In this study, the planetary ball milling with CaO addition was used to remediate lindane-contaminated soil. Based on Hertzian theory, a mathematical model was proposed to simulate the trajectory of grinding ball and the local energy transfer during a planetary operation at the disk rotation velocities of 150-250 rpm. Besides, the influence of different parameters on lindane removal in soil was investigated, whose results showed that disk rotation velocity and reagent-to-soil ratio had a positive effect, while soil moisture, initial concentration of lindane, and mass of polluted soil demonstrated a negative influence. The mechanochemical method exhibited a higher degradation performance at 3 wt% CaO addition, and a disk rotation velocity of 250 rpm. Active species generated by ball collisions in the presence of CaO, especially superoxide (·O2-) demonstrated a significant role in participating in the lindane conversion. In combination with GCMS and XPS analysis, the proposed model provides insight into mechanochemical remediation process from physical and chemical perspectives, which mainly includes four main steps: mixing, inducing, chemical reaction, and structure destruction.

14.
Chemosphere ; 361: 142516, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850691

RESUMO

Activated siderite, endowed with excellent properties, was simply prepared by co-grinding with Fe sulfate to enhance its high reducing ability for Cr(VI). Batch experiments were conducted to investigate the main affecting parameters, such as material ratio, pH, temperature, etc. The removal of Cr(VI) by activated siderite was completed within 4 h of the reaction. The activated siderite maintained a high removal effect of Cr(VI) within a wide pH range (3-9). Various analytical methods, including XRD, SEM/EDS, XPS, etc., were employed to characterize the samples and discover variations before and after the reaction. The Fe (Ⅱ) in activated siderite becomes highly active, and it can even be released from the solid phase in the mildly acidic liquid phase to efficiently reduce Cr(VI) and mitigate its toxicity. These findings introduce an innovative approach for activating various minerals widely distributed in nature to promote the recovery of the ecological system.


Assuntos
Cromo , Compostos Férricos , Oxirredução , Cromo/química , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Ferro/química , Compostos Ferrosos/química , Minerais/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Carbonatos
15.
ChemSusChem ; : e202401055, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924618

RESUMO

The development of green and environmentally friendly synthesis methods of electrocatalysts is a crucial aspect in decarbonizing energy generation. In this study, eco-friendly mechanochemical synthesis of perovskite metal oxide-carbon black composites is proposed using different conditions and additives such as KOH. Furthermore, the optimization of ball milling conditions, including time and rotational speed, is studied. The mechanochemical synthesis in solid-state conditions without additives produces electrocatalysts that exhibit the highest bifunctional electrochemical activity towards both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Moreover, this synthesis demonstrates a lower Environmental Impact Factor (E-factor), indicating its greener nature, and due to its simplicity, it has a great potential for scalability. The obtained bifunctional electrocatalysts have been tested in a rechargeable zinc-air battery (ZAB) for 22 h with similar performance compared to the commercial catalyst (Pt/C) at significantly lower cost. These promising findings are attributed to the enhanced interaction between the perovskite metal oxide and carbon material and the improved dispersion of the perovskite metal oxide on the carbon materials.

16.
Angew Chem Int Ed Engl ; : e202406103, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818671

RESUMO

Fundamental understanding of mechanochemical reactivity is important for designing new mechanophores. Besides the core structure of mechanophores, substituents on a mechanophore can affect its mechanochemical reactivity through electronic stabilization of the intermediate or effectiveness of force transduction from the polymer backbone to the mechanophore. The latter factor represents a unique mechanical effect in considering polymer mechanochemistry. Here, we show that regioisomeric linkage that is not directly adjacent to the first cleaving bond in cyclobutane can still significantly affect the mechanochemical reactivity of the mechanophore. We synthesized three non-scissile 1,2-diphenyl cyclobutanes, varying their linkage to the polymer backbone via the o, m, or p-position of the diphenyl substituents. Even though the regioisomers share the same substituted cyclobutane core structure and similar electronic stabilization of the diradical intermediate from cleaving the first C-C bond, the p isomer exhibited significantly higher mechanochemical reactivity than the o and m isomers. The observed difference in reactivity can be rationalized as the much more effective force transduction to the scissile bond through the p-position than the other two substitution positions. These findings point to the importance of considering force-bearing linkages that are more distant from the bond to be cleaved when incorporating mechanophores into polymer backbones.

17.
Nanomaterials (Basel) ; 14(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38727334

RESUMO

Amorphous silica particles (ASPs) have been reported to exhibit bioactive properties and are becoming the focus of attention as bioceramics. However, their interactions with proteins in living organisms remain to be understood and need to be investigated in order to achieve wider applications. Our research group found that chlorine (Cl)-containing ASPs are useful for protein immobilization. Photofunctional dyes (fluorescein (FS-), methylene blue (MB+)) that have the carboxy and amino groups as the main functional groups were immobilized on the Cl-containing ASPs via the mechanochemical method as the model molecule and their spectral properties were used to investigate and discuss the organic/inorganic interfacial bonding states. In FS-, the oxygen atoms of the carboxy groups in the molecule were immobilized by the hydrogen bonds with the silanol groups on the ASPs surfaces, indicating that there is an optimum Cl content for the immobilization as the monomer state. In the case of MB+, as the Cl concentration in the ASPs increases, the immobilization via the electrostatic interactions between the Cl in the ASPs and the terminal dimethylamino group, and the hydrogen bonding between the N atoms of the MB+ hetero ring and the particle silanol group were enhanced. These results mainly suggest that the protein adsorption system occurs through the hydrogen bonding between the carboxy groups of the protein and the silanol groups on the particles and via electrostatic interactions between the amino groups of the protein and the dissociated silanol groups and the contained Cl at the particles. Thus, the spectral characterization using dyes as probes is expected to predict the protein interactions with the amorphous silica particles.

18.
J Vasc Surg Venous Lymphat Disord ; : 101902, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754778

RESUMO

OBJECTIVE: The purpose of this study was to compare the clinical outcomes of radiofrequency ablation (RFA), cyanoacrylate closure (CAC), mechanochemical ablation (MOCA), and surgical stripping (SS) for incompetent saphenous veins and to determine a suitable treatment modality for a specific clinical situation. METHODS: We retrospectively reviewed the data of patients with varicose veins who underwent RFA, CAC, MOCA, or SS from January 2012 to June 2023. The clinical outcomes, including postoperative complications and the Aberdeen Varicose Vein Questionnaire score, were assessed. RESULTS: During the study period, 2866 patients with varicose veins were treated. Among them, 1670 patients (57.9%) were women. The mean age was 55.3 ± 12.9 years. RFA, CAC, MOCA, and SS were performed in 1984 (68.7%), 732 (25.4%), 78 (2.7%), and 88 (3.0%) patients, respectively. The complete target vein closure rate after RFA, CAC, and MOCA was 94.5%, 98%, and 98%, respectively. The absence of a target vein after SS was 98%. Deep vein thrombosis developed in four patients: one in the RFA group and three in CAC group. Surgical or endovenous procedure-induced thrombosis occurred in 2.3%, 4.8%, 6.4%, and 2.3% of the patients after RFA, CAC, MOCA, and SS, respectively. Phlebitis along the target vein occurred in 0.2% and 3.8% of patients after RFA and MOCA, respectively. A hypersensitivity reaction occurred in 3.7% of patients after CAC. Readmission was required for two patients who had undergone SS. Transient nerve symptoms developed in five (0.3%), zero, one (1.3%), and two (2.3%) patients after RFA, CAC, MOCA, and SS, respectively. After treatment, the Aberdeen Varicose Vein Questionnaire score improved significantly in all groups. CONCLUSIONS: The clinical outcomes with improvement in quality of life were comparable among the different treatment modalities. The proximity of the nerve or skin to the target vein is the most important factor in selecting a suitable treatment modality.

19.
Cell Mol Bioeng ; 17(2): 137-151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38737453

RESUMO

Introduction: Kinesin-3 motor, which is in the monomeric and inactive form in solution, after cargo-induced dimerization can step on microtubules towards the plus end with a high velocity and a supperprocessivity, which is responsible for transporting the cargo in axons and dendrites. The kinesin-3 motor has a large initial landing rate to microtubules and spends the majority of its stepping cycle in a one-head-bound state. Under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor. Methods: To understand the physical origin of the peculiar features for the kinesin-3 motor, a model is presented here for its chemomechanical coupling. Based on the model the dynamics of the motor under no load, under the ramping load and under the constant load is studied analytically. Results: The theoretical results explain well the available experimental data under no load and under the ramping load. For comparison, the corresponding available experimental data for the kinesin-1 motor under the ramping load are also explained. The predicted results of the velocity, dissociation rate and run length versus the constant load for the kinesin-3 motor are provided. Conclusions: The study has strong implications for the chemomechanical coupling mechanism of the kinesin-3 dimer. The origin of the kinesin-3 dimer in the predominant one-head-bound state is due to the fact that the rate of ATP transition to ADP in the trailing head is much larger than that of ADP release from the MT-bound head. The study shows that the kinesin-3 ADP-head has an evidently longer interaction distance with microtubule than the kinesin-1 ADP-head, explaining why in the initial ADP state the kinesin-3 motor has the much larger landing rate than the kinesin-1 motor and why under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-024-00795-1.

20.
AAPS PharmSciTech ; 25(4): 84, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605282

RESUMO

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1 h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.


Assuntos
Telmisartan , Cristalização , Solubilidade , Estabilidade de Medicamentos
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