Computational Study Research Articles

A computational study of how an α- to γ-motoneurone collateral can mitigate velocity-dependent stretch reflexes during voluntary movement

A computational study of how an α- to γ-motoneurone collateral can mitigate velocity-dependent stretch reflexes during voluntary movement

Postsynthetically Modified Cationic, Robust MOF Featuring Selective Separation of Carboxylate-Containing Pharmaceutical Drugs from Water at Neutral pH: Elucidation of the Adsorption Mechanism by Theory and Experiments.

The escalating levels of hazardous pharmaceutical contaminants, specifically nonsteroidal anti-inflammatory drugs (NSAIDs), in groundwater reservoir surfaces and surface waterway systems have prompted substantial scientific interest regarding their potential deleterious effects on both aquatic ecosystems and human health. Extraction of those pollutants from wastewater is quite challenging. Hence, the development of economic, sustainable, and scalable techniques for capturing and removing those pollutants is crucial to ensure water safety. Herein, we demonstrate a physicochemically stable, reusable, porous Hf(IV)-based cationic metal-organic framework (MOF), namely, 1'@MeCl for the aqueous phase adsorption-based removal of NSAIDs (diclofenac, naproxen, ibuprofen) from the wastewater environment. The highly positively charged surface of the 1'@MeCl MOF enables it to selectively extract more than 99% of diclofenac, naproxen, and ibuprofen contaminants within less than 30 s. With fast adsorption kinetics, very high adsorption capacities (Qe) were achieved at neutral pH for diclofenac (482.9 mg/g), naproxen (295.9 mg/g), and ibuprofen (219.5 mg/g). Moreover, the influence of changes in pH and coexisting anions on the adsorption property of the 1'@MeCl MOF was studied. Furthermore, the adsorption efficiency of 1'@MeCl in different real water environments was ensured by performing diclofenac, naproxen, and ibuprofen adsorption from tap, river, and lake water. Moreover, a 1'@MeCl-anchored cellulose acetate-chitosan membrane was developed successfully to demonstrate the membrane-based extraction of diclofenac, naproxen, and ibuprofen from contaminated water. Furthermore, a molecular-level mechanistic study was performed through experimental and computational study to propose the plausible adsorption mechanisms for diclofenac, naproxen, and ibuprofen over the surface of 1'@MeCl.

Computational Study on the Effects of Valve Orientation on the Hemodynamics and Leaflet Dynamics of Bioprosthetic Pulmonary Valves.

Pulmonary valves do not display a fibrous annulus as do other valves in the heart; thus, pulmonary valves can be implanted at multiple orientations and locations within the right ventricular outflow tract (RVOT). This gives surgeons more freedom when implanting the valve but it also results in uncertainties regarding placement, particularly with respect to valve orientation. We investigate the pulmonary artery hemodynamics and valve leaflet dynamics of PVRs with various orientations via fluid-structure interaction models. A canonical model of the branching pulmonary artery is coupled with a dynamic model of a pulmonary valve and from this, we quantify the effect of valve implant orientation on the post-valvular hemodynamics and leaflet dynamics. Metrics such as turbulent kinetic energy, branch pulmonary artery flow distributions, projected valve opening area, and pressure differentials across the valve leaflets are analyzed. Our results indicate that off-axis orientation results in higher pressure forces and flow and energy asymmetry, which potentially have implications for long term durability of implanted bioprosthetic valves.

Exploring the Anticancer Potential of Furanpydone A: A Computational Study on its Inhibition of MTHFD2 Across Diverse Cancer Cell Lines.

Cancer poses a significant global health challenge due to its high mortality rate and complex treatment strategies. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), which is notably overexpressed in various malignancies, represents a promising target for anticancer drug development. Furanpydone A, a new 4-hydroxy-2-pyridone alkaloid isolated from the endophytic fungus Arthrinium sp. GZWMJZ-606, has shown potent inhibitory activity against several cancer cell lines. This study provides the first computational evaluation of furanpydone A, focusing on its potential inhibition of MTHFD2 through molecular docking and 200 ns molecular dynamics (MD) simulations. Molecular docking revealed a binding free energy of -8.08 kcal/mol for furanpydone A, comparable to the control compound DS44960156 (-8.13 kcal/mol), indicating stable interactions with the MTHFD2 active site. MD simulations confirmed the structural stability of the furanpydone A-MTHFD2 complex, with RMSD values ranging from 1.5 to 2.9 Å, RMSF values below 4 Å, and a radius of gyration (Rg) of 26.7 Å. Furanpydone A maintained approximately four consistent hydrogen bonds throughout the simulation. Analysis of furanpydone A binding pose orientations and interactions with the MTHFD2 enzyme at 0 ns, 40 ns, 80 ns, 120 ns, 160 ns, and 200 ns revealed consistent and stable binding. MM-PBSA analysis showed a binding free energy (ΔGbind) of -23.57 ± 0.13 kcal/mol, with electrostatic and van der Waals interactions contributing significantly, suggesting competitive binding affinity to the control compound (-25.32 ± 0.11 kcal/mol). The contribution of individual amino acid residues, including key residues such as ARG43, TYR84, ASN87, LYS88, GLN132, and PRO314, indicated strong interactions that support the stability of the furanpydone A-MTHFD2 complex. ADMET predictions indicated that furanpydone A met key drug-likeness criteria and demonstrated good oral bioavailability, suitable distribution profile, minimal risk of drug-drug interactions, efficient elimination, and low toxicity potential. These findings suggest that furanpydone A is a promising candidate for cancer treatment, warranting further in vitro and in vivo validation, and highlighting its potential impact on the development of new anticancer therapies.

Iridium-Catalyzed Oxidant-Free Transfer Dehydrogenation of Carboxylic Acids.

Direct dehydrogenation of carboxylic acids to their unsaturated counterparts represents a valuable transformation for complex molecule synthesis, which, however, has been challenging to achieve. In addition, the current carbonyl desaturation methods are almost all based on oxidative conditions. Here we report an Ir-catalyzed redox-neutral transfer dehydrogenation approach to directly convert carboxylic acids to either α,β- or β,γ-unsaturated counterparts. These reactions avoid using oxidants or strong bases, thus, tolerating various functional groups. The combined experimental and computational mechanistic studies suggest that this transfer hydrogenation reaction involves directed C-H oxidative addition, β-H elimination, and dihydride transfer to an alkene acceptor with C(sp3)-H reductive elimination as the turnover-limiting step.

Heat transfer characteristics of printed circuit heat exchangers under mechanical vibrations

Purpose The purpose of this paper is to investigate the impact of mechanical vibration on the heat transfer and pressure drop characteristics of semicircular channel printed circuit heat exchangers (PCHEs), while also establishing correlations between vibration parameters and thermal performance. Design/methodology/approach By combining experimental and numerical simulation methods, the heat transfer coefficient and pressure drop characteristics of supercritical carbon dioxide (S-CO2) in a semicircular channel with a diameter of 2 mm under vibration conditions were studied. Reinforce the research by conducting computational fluid dynamics studies using ANSYS Fluent 22.0, the experimental results were compared with the numerical simulation results to verify the accuracy of the numerical method. Findings The use of vibration has the potential to attenuate the degradation of wall heat transfer caused by buoyancy-induced PCHEs on the upward-facing surface. The heat transfer enhancement (HTE) was maximized by an increase of 18.2%, while the pressure drop enhancement (PDE) was elevated by over 25-fold. The capacity to enhance the heat exchange between S-CO2 and channel walls through increasing vibration intensity is limited, indicating maximum effectiveness in improving thermal performance. Originality/value Conducting heat transfer experiments on PCHEs with mechanical vibration enhancement and verifying the accuracy of the vibration numerical model. The relation based on the dimensionless factor is derived. To provide theoretical support for using vibration to enhance the heat transfer capability of PCHEs.

Multiscale Computational Study of Cellulose Acetate-Water Miscibility: Insights from Molecularly Informed Field-Theoretic Modeling.

Cellulose acetate (CA), a prominent water-soluble derivative of cellulose, is a promising biodegradable ingredient that has applications in films, membranes, fibers, drug delivery, and more. In this work, we present a molecularly informed field-theoretic model for CA to explore its phase behavior in aqueous solutions. By integrating atomistic details into large-scale field-theoretic simulations via the relative entropy coarse-graining framework, our approach enables efficient calculations of CA's miscibility window as a function of the degree of substitution (DS) of cellulose hydroxyl groups with acetate side chains. This allows us to capture the intricate phase behavior of CA, particularly its unique miscibility at intermediate substitution, without relying on experimental input. Additionally, the model directly probes CA solution behavior specific to the relative DS at C2, C3, and C6 alcohol sites, providing insights for the rational design of water-soluble CA for diverse applications. This work demonstrates a promising integration of molecularly informed field theories, complementing wet-lab experimentation, for engineering the next-generation polymeric materials with precisely tailored properties.

Microwave-assisted fabrication of high-strength natural fiber hybrid composites for sustainable applications: An experimental and computational study

The present study deals with the fabrication of hybrid composites using biodegradable and ecologically friendly natural fibers and a recyclable thermoplastic matrix. Pure and hybrid natural fiber composites of high-density polyethylene (HDPE) with Kenaf and Ramie fiber, 20 wt%, were fabricated using microwave-assisted compression molding. The composite's mechanical characterization was performed using tensile, flexural, impact, and hardness tests. X-ray diffraction was done to investigate the crystallinity percentage, and scanning electron microscopy of fractured surfaces was performed to determine failure mechanisms. The hybrid composite of HDPE/Ramie and Kenaf exhibited the highest ultimate tensile strength (UTS) at 29.3 ± 1.2 MPa, surpassing HDPE/Kenaf (21.6 ± 1.1 MPa) and HDPE/Ramie (24.3 ± 1.4 MPa) composites. In terms of flexural strength, HDPE/Ramie demonstrated the highest at 19.9 ± 1.5 MPa, while HDPE/Kenaf had the lowest at 18 ± 1.1 MPa. The hybrid composite's flexural strength was intermediate at 19 ± 1.3 MPa. Impact strength followed a similar trend, with the hybrid composite leading at 40.2 KJ/m2, followed by HDPE/Ramie (26.9 KJ/m2) and HDPE/Kenaf (12.3 KJ/m2). Hardness tests revealed the highest hardness in the hybrid composite and the lowest in HDPE/Kenaf. A computational study has been performed to develop a model for predicting the hybrid composites. A strong agreement between both studies has been observed. The developed composite is deemed suitable for various light-duty applications, such as roofing, car interior panels, and mobile covers, offering potential benefits in reducing carbon footprint.

Synthesis, X-ray Crystallography, Spectroscopic Characterizations, Density Functional Theory, and Hirshfeld Surface Analyses of a Novel (Carbonato) Picket Fence Iron(III) Complex

An Fe(III)-carbonato six-coordinate picket fence porphyrin complex with the formula [K(2,2,2-crypt)][FeIII(TpivPP)(CO3)]·C6H5Cl·3H2O (I) has been synthesized and characterized by UV-Vis and FT-IR spectra. The structure of (carbonato)(α,α,α,α-tetrakis(o-pivalamidophenyl)porphinato)ferrate(III) was also established by XRD. The iron atom is hexa-coordinated by the four nitrogen atoms of the pyrrol rings and the two oxygen atoms of the CO32− group. Complex I, characterized as a ferric high-spin complex (S = 5/2), presented higher Fe-Np (2.105(6) Å) and Fe-PC (0.654(2) Å) distances. Both X-ray molecular structure and Hirshfeld surface analysis results show that the crystal packing of I is made by C-H⋯O and C-H⋯Cg weak intermolecular hydrogen interactions involving neighboring [FeIII(TpivPP)(CO3)]− ion complexes. Computational studies were carried out at DFT/B3LYP-D3/LanL2DZ to investigate the HOMO and LUMO molecular frontier orbitals and the reactivity within the studied compound. The stability of compound I was investigated by analyzing both intra- and inter-molecular interactions using the 2D and 3DHirshfeld surface (HS) analyses. Additionally, the frontier molecular orbital (FMO) calculations and the molecular electronic potential (MEP) analyses were conducted to determine the electron localizations, electrophilic, and nucleophilic regions, as well as charge transfer (ECT) within the studied system.

Thionation‐Induced Enhancement of Optical and Electronic Properties in NDI Molecule for Molecular Electronic Applications: A Computational Study Using DFT/TD‐DFT and QTAIM Theory

AbstractThe study investigates the impact of thionation on N,N'‐di(dodecyl)‐4,5,8,9‐naphthalene diimide (NDI) through computational methods such as density functional theory (DFT/TD‐DFT), quantum theory of atoms in molecules (QTAIM), and Landauer theory (LT). Thionation, involving the replacement of diamide oxygens with sulfurs in NDI, significantly enhances quantum‐electronic/thermoelectric properties. Computational analyzes of energy of frontier orbitals HOMO/LUMO, dipole moment, polarizability, first superpolarizability, UV spectrum, and cohesive energy show the superior performance of the thione structure (M2) compared to the pristine structure (M1). Thionation decreased the energy gap from 01.3 eV (in M1 structure) to 1.87 eV (in M2 structure). The absorption wavelength in the pristine structure (M1) is calculated to be 507 nm, which increased to 1067 nm after thionation (M2). Cohesive energy values for each of M1 and M2 structures are calculated as 12.76 and 12.89 Kcal mol−1, respectively, which indicates the improvement of stability after thionation. After connecting M1 and M2 to gold electrodes (Au‐M1‐Au and Au‐M2‐Au) and applying electric fields, the Au‐M2‐Au structure shows a lower energy gap, lower thermoelectric activity and higher conductivity at field intensities with higher than 140 × 10−4 (a.u.), indicating its use as a field‐effect molecular device (such as molecular wire or molecular switch).

Instances of bias: the gendered semantics of generic masculines in German revealed by instance vectors

Abstract While research using behavioural methods has repeatedly shown that generic masculines in German come with a male bias, computational methods only entered this area of research very recently. The present paper shows that some assumptions made by these recent computational studies – treating genericity as an inflectional function and computing a vector for generic usage strongly correlated with the grammatical masculine – are not without issue, and offers the use of semantic instance vectors as a possible solution to these issues. Beyond this methodological improvement, the present paper finds that generic masculines are indeed semantically more similar to specific masculines than to specific feminines – results that are in line with findings by the recent computational studies and the majority of previous behavioural studies.

Phenalenyl-ruthenium synergism for effectual catalytic transformations of primary amines to amides.

The synthesis of amides holds great promise owing to their impeccable contributions as building blocks for highly valued functional derivatives. Herein, we disclose the design, synthesis and crystal structure of a mixed-ligand ruthenium(II) complex, [Ru(η6-Cym)(O,O-PLY)Cl], (1) where Cym = 1-isopropyl-4-methyl-benzene and O,O-PLY = deprotonated form of 9-hydroxy phenalenone (HO,O-PLY). The complex catalyzes the aerobic oxidation of various primary amines (RCH2NH2) to value-added amides (RCONH2) with excellent selectivity and efficiency under relatively mild conditions with common organic functional group tolerance. Structural, electrochemical, spectroscopic, and computational studies substantiate that the synergism between the redox-active ruthenium and π-Lewis acidic PLY moieties facilitate the catalytic oxidation of amines to amides. Additionally, the isolation and characterization of key intermediates during catalysis confirm two successive dehydrogenation steps leading to nitrile, which subsequently transform to the desired amide through hydration. The present synthetic approach is also extended to substitution-dependent tuning at PLY to tune the electronic nature of 1 and to assess substituent-mediated catalytic performance. The effect of substitution at the PLY moiety (5th position) leads to structural isomers, which were further evaluated for the catalytic transformations of amine to amides under similar reaction conditions.

Azobenzenesulfonamide Carbonic Anhydrase Inhibitors as New Weapons to Fight Helicobacter pylori: Synthesis, Bioactivity Evaluation, In Vivo Toxicity, and Computational Studies

Research into novel anti-Helicobacter pylori agents represents an important approach for the identification of new treatments for chronic gastritis and peptic ulcers, which are associated with a high risk of developing gastric carcinoma. In this respect, two series of azobenzenesulfonamides were designed, synthesized, and tested against a large panel of human and bacterial CAs to evaluate their inhibitory activity. In addition, computational studies of the novel primary benzenesulfonamides (4a–j) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus H. pylori of the two series was also studied. The best-in-class compounds were found to be 4c and 4e among the primary azobenzenesulfonamides and 5c and 5f belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti-H. pylori activity, with MIC values of 4–8 μg/mL and MBCs between 4 and 16 μg/mL. Moreover, the evaluation of their toxicity on a G. mellonella larva in vivo model indicated a safe profile for 4c,e and 5c,f. The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti-H. pylori agents.

Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.

Human somatic angiotensin-converting enzyme (ACE) is a key zinc metallopeptidase that plays a pivotal role in the renin-angiotensin-aldosterone system (RAAS) by regulating blood pressure and electrolyte balance. Inhibition of ACE is a cornerstone in the management of hypertension, cardiovascular diseases, and renal disorders. Recent advances in structural biology techniques have provided invaluable insights into the molecular mechanisms underlying ACE inhibition, facilitating the design and development of more effective therapeutic agents. This review focuses on the latest advancements in elucidating the structural basis for ACE inhibition. High-resolution crystallographic studies of minimally glycosylated individual domains of ACE have revealed intricate molecular details of the ACE catalytic N- and C-domains, and their detailed interactions with clinically relevant and newly designed domain-specific inhibitors. In addition, the recently elucidated structure of the glycosylated form of full-length ACE by cryo-electron microscopy (cryo-EM) has shed light on the mechanism of ACE dimerization and revealed continuous conformational changes which occur prior to ligand binding. In addition to these experimental techniques, computational approaches have also played a pivotal role in elucidating the structural basis for ACE inhibition. Molecular dynamics simulations and computational docking studies have provided atomic details of inhibitor binding kinetics and energetics, facilitating the rational design of novel ACE inhibitors with improved potency and selectivity. Furthermore, computational analysis of the motions observed by cryo-EM allowed the identification of allosteric binding sites on ACE. This affords new opportunities for the development of next-generation allosteric inhibitors with enhanced pharmacological properties. Overall, the insights highlighted in this review could enable the rational design of novel ACE inhibitors with improved efficacy and safety profiles, ultimately leading to better therapeutic outcomes for patients with hypertension and cardiovascular diseases.

Retinal Degeneration Response to Graphene Quantum Dots: Disruption of the Blood-Retina Barrier Modulated by Surface Modification-Dependent DNA Methylation.

Graphene quantum dots (GQDs) are used in diverse fields from chemistry-related materials to biomedicines, thus causing their substantial release into the environment. Appropriate visual function is crucial for facilitating the decision-making process within the nervous system. Given the direct interaction of eyes with the environment and even nanoparticles, herein, GQDs, sulfonic acid-doped GQDs (S-GQDs), and amino-functionalized GQDs (A-GQDs) were employed to understand the potential optic neurotoxicity disruption mechanism by GQDs. The negatively charged GQDs and S-GQDs disturbed the response to light stimulation and impaired the structure of the retinal nuclear layer of zebrafish larvae, causing vision disorder and retinal degeneration. Albeit with sublethal concentrations, a considerably reduced expression of the retinal vascular sprouting factor sirt1 through increased DNA methylation damaged the blood-retina barrier. Importantly, the regulatory effect on vision function was influenced by negatively charged GQDs and S-GQDs but not positively charged A-GQDs. Moreover, cluster analysis and computational simulation studies indicated that binding affinities between GQDs and the DNMT1-ligand binding might be the dominant determinant of the vision function response. The previously unknown pathway of blood-retinal barrier interference offers opportunities to investigate the biological consequences of GQD-based nanomaterials, guiding innovation in the industry toward environmental sustainability.

Boosting the Efficiency of Red Thermally Activated Delayed Fluorescence via Conjugation Enhancement in Push-Pull Naphthalimide Derivatives.

In this work, we synthesize a series of push-pull compounds bearing naphthalimide as the electron acceptor and tetraphenylethylene (TPE)/triphenylamine (TPA)/phenothiazine (PTZ) as the electron rich/electron donor units. These moieties are arranged in highly conjugated quadrupolar structures. The structure-property relationships are investigated through a joint experimental time-resolved spectroscopic and computational TD-DFT study. The femtosecond transient absorption and fluorescence up-conversion experiments reveal ultrafast photoinduced intramolecular charge transfer. This is likely the key factor leading to efficient spin-orbit CT-induced intersystem crossing for the TPA- and PTZ-derivatives as well as to small singlet-to-triplet energy gap. Consequently, evidence for a delayed fluorescence component is found together with the main prompt emission in the fluorescence kinetics both in solution and in thin film. The weight of the Thermally Activated Delayed Fluorescence (TADF) is greatly enhanced when these fluorophores are used as guests in solid-state host matrices. TADF is interestingly revealed in the orange-red region of the visible. Such long wavelength emission is here observed with surprisingly large fluorescence quantum yields, thanks to the conjugation enhancement achieved in these newly synthesized structures relative to previous studies. Our findings may be thus promising for the future development of efficient third generation TADF-based OLEDs.

Transition Metal Mimetic π-Activation by Cationic Bismuth(III) Catalysts for Allylic C-H Functionalization of Olefins Using C═O and C═N Electrophiles.

The discovery and utilization of main-group element catalysts that behave similarly to transition metal (TM) complexes have become increasingly active areas of investigation in recent years. Here, we report a series of Lewis acidic bismuth(III) complexes that allow for the catalytic allylic C(sp3)-H functionalization of olefins via an organometallic complexation-assisted deprotonation mechanism to generate products containing new C-C bonds. This heretofore unexplored mode of main-group reactivity was applied to the regioselective functionalization of 1,4-dienes and allylbenzene substrates. Experimental and computational mechanistic studies support the key steps of the proposed catalytic cycle, including the intermediacy of elusive Bi-olefin complexes and allylbismuth species.

LiNbO3 and LiTaO3 Coating Effects on the Interface of the LiCoO2 Cathode: A DFT Study of Li-Ion Transport.

In solid-state batteries, the interface between cathodes and solid electrolytes is crucial and coating layers play a vital role. LiNbO3 has been known as a promising coating material, whereas recent studies showed its degradation via releasing oxygen and lithium during cycling. This computational study addresses the elucidation of essential characteristics of the coating materials by examining LiNbO3 and its counterpart LiTaO3 interfaces to a representative layered cathode, LiCoO2. Employing the interface CALYPSO method, we constructed explicit models of both coatings on LiCoO2. Our findings indicate that LiTaO3 offers easier Li+ migration at the interface due to the smaller difference in Li adiabatic potential at the interface, whereas LiNbO3 more effectively suppresses oxygen activity at high delithiation states via lowering the O 2p states. This comparative analysis provides essential insights into optimizing coating materials for improved battery performance.

Enhancing heat exchanger performance with perforated/non‐perforated flow modulators generating continuous/discontinuous swirl flow: A comprehensive review

AbstractHeat exchangers are crucial in transferring heat and finding applications across various industries. Numerous strategies have been devised to improve and optimize the heat transfer process within these systems. Among these, passive methods have garnered significant attention for their ability to operate without external power consumption. This article examines the recent experimental and computational studies conducted by researchers since 2018 on passive enhancement techniques, especially twisted tape, wire coil, swirl flow generator, and others, to boost the thermal efficiency of heat exchangers and aid designers in adopting passive augmentation methods for compact heat exchangers. Recently, researchers' new class of flow maldistribution devices, referred to as swirl flow devices, has gained attention; which enhances convective heat transfer by introducing swirl into the main flow and disrupting the boundary layer at the tube surface through alterations in surface geometry. Twisted tape inserts are devices that demonstrate better performance in laminar flow compared to turbulent flow. Conversely, other passive techniques like ribs, conical nozzles, and conical rings are generally more effective in turbulent flow than laminar flow. A recent research trend is the utilization of nanofluids in combination with other passive heat transfer enhancement techniques like turbulators, ribs, and twisted tape inserts in heat exchangers, which can reduce exergy losses and improve overall convective heat transfer coefficient and effectiveness of heat exchanger.

Computational Study of the Ir-Catalyzed Formation of Allyl Carbamates from CO2

Computational Study of the Ir-Catalyzed Formation of Allyl Carbamates from CO₂