Browse Articles

Natural talc: a basic, cost-effective, and available catalyst for the one-pot synthesis of dihydropyranochromenes and pyranopyrazoles, along with related DFT calculations

Abstract This study investigates environmentally friendly and efficient protocols for synthesizing two distinct heterocyclic scaffolds: pyranopyrazoles and dihydropyranochromenes. Dihydropyranochromenes were synthesized using talc in refluxing ethanol, while pyranopyrazoles were obtained from solvent-free under mixing conditions. The advantages of these methods include high yields, operability, and the use of an accessible, inexpensive, and non-toxic basic catalyst. The reaction conditions, including reaction time, molar ratios of reactants, and catalyst amount, were optimized for the synthesis of products, resulting in high yields of 97% for pyranopyrazoles and 95% for dihydropyranochromenes. The synthesized products were characterized using analytical techniques, including FTIR and NMR, which confirmed the successful synthesis. In this study, total energy and band gap energy calculations were performed for dihydropyranochromenes and pyranopyrazoles derivatives. This suggests that talc powder a natural catalyst, can enhance organic synthesis and offer a sustainable and environmentally friendly solution for modern organic chemistry.

Static and dynamic properties of a binary, symmetric mixture of ultrasoft particles in the vicinity of criticality

We investigate the static and the dynamic properties of a binary, equimolar, size-symmetric mixture of ultrasoft particles in the vicinity of the critical point of the system. Based on the generalized exponential potential (GEM) of order four for the particle interaction and using extensive molecular dynamics simulations in the canonical ensemble, we investigate the above-mentioned properties for various scenarios: we consider several supercritical and subcritical states, and we expose the system to rapid quenches and to external shearing forces. Based on an accurate determination of the phase diagram and of the location of the critical point, we study the static structure of the system in terms of particle-based radial distribution functions. As systems of GEM particles are prone to cluster formation, we complement these investigations with a detailed analysis of the composition of the clusters and of their spatial correlations for the different scenarios introduced above. Furthermore, we analyze the temperature dependence of the diffusivity of the particles and the shear viscosity of the system. All these data provide a detailed and profound insight into the properties of the system under phase separation conditions and near criticality.

Climate-driven flood hazard assessment in data-scarce mountainous basins using a GIS-based machine learning and hydrodynamic modelling under CMIP6 SSP scenarios

Non-equilibrium Trajectory Sampling (NETS) method for generating free-energy landscapes and steady-state distributions

This study presents a novel method for constructing free-energy profiles and steady-state distributions from either equilibrium or non-equilibrium trajectories along a defined reaction coordinate. The method works by tracking the final states of a swarm of short simulations launched under different initial conditions with no prior knowledge of the free energy landscape. Subsequently, this trajectory information is used to build a transition matrix whose primary eigenvector captures the steady-state occupation probability for each value of the reaction coordinate, yielding the free energy profile in equilibrium. This innovative method holds potential for many new materials and engineering applications where it is desired to know the free energy of rate-limiting configurations as may be relevant for transport processes (in, e.g., battery electrolytes and nano-filtration membranes), complexation (in, e.g., self-assembly and ligand-binding interactions), or in tuning properties such as adsorption. We illustrate the effectiveness of the method by capturing the free energy associated with a one-dimensional barrier potential modeling a separation membrane and the particle distribution associated with thermophoresis under a temperature gradient. Further extensions and applications of the method are also discussed.

Mechanistic insights into dissolution enhancement of co-spray dried meloxicam with chitosan and solubilization agent

Abstract This study presents a co-spray drying formulation approach to enhance the dissolution rate of meloxicam (MX), a poorly soluble model drug, by combining it with chitosan (CHIT) and sodium lauryl sulfate (SLS). Ternary formulations were prepared using both mini- and medium-scale spray dryers and compared with physical mixtures and RAW MX. In vitro dissolution testing revealed a significant increase in the release rate, with up to 80% of MX dissolved within 5 min. A comprehensive set of solid-state analytical techniques (XRPD, FTIR, and confocal Raman microscopy) revealed subtle changes in MX crystallinity and hydrogen-bonding interactions with both excipients. These findings support three key mechanisms contributing to enhanced dissolution: (i) reduced agglomeration of MX via adsorption onto the CHIT surface, (ii) improved wettability of products due to the presence of SLS, and (iii) increased matrix hydrophilicity facilitating drug–medium contact. The successful scale-up using a medium-scale spray dryer demonstrated the feasibility of this strategy for industrial application. The results highlight co-spray drying with functional excipients as a robust and scalable method for improving the biopharmaceutical performance of poorly soluble drugs. The simple co-spraying of the CHIT dispersion with the drug solution, without the need to dissolve the chitosan, is additional advantage.

A semi-focused multi-state variant of the mapping approach to surface hopping

The mapping approach to surface hopping (MASH) is one of the most promising methods for simulating nonadiabatic dynamics in molecular systems, in a mixed quantum/classical framework. In its original formulation, MASH is limited to the treatment of two-state systems. Here, we present a generalization of MASH to multiple electronic states, which we call semi-focused MASH (SMASH). A key distinguishing aspect of our approach is that only a selected subset of electronic states, identified through an appropriate clustering procedure, is initially populated. Test simulations of the ultrafast photodynamics of three molecular systems (spiropyran, thioguanine, and azobenzene) show that SMASH gives results closely matching those of decoherence-corrected fewest-switches surface hopping, while eliminating the need for the ad hoc decoherence correction.

Elevated liver enzyme trajectories in early adulthood and persistently high levels predict type 2 diabetes risk in Japanese adults

Fourier-transform infrared spectroscopy of hydrogen fluoride dimers in solid parahydrogen

We investigate the Fourier-transform infrared spectra of hydrogen fluoride dimers in solid parahydrogen, the detailed analysis of which has remained unexplored. We propose a plausible analysis based on concentration dependence, light polarization, annealing, and time evolution. The absorption lines exhibited multiple peaks, with intensity ratios significantly altered by annealing and by time evolution at a constant temperature. The spectral patterns and isotopic effects suggest that the dimers do not rotate freely in solid parahydrogen, while multiple peaks arise from different stable structures, including single and double substitution sites. Unlike in the gas phase and helium droplets, no tunneling splitting was observed. The broad ν1 band suggests that some dimer structures may exhibit axial rotation. Spectral changes due to annealing likely result from site conversion, while observed IR-induced changes indicate preferential dissociation of dimers in double substitution sites. These findings still remain tentative, necessitating further experimental and theoretical studies.

A denoising method for aeroengine gas path electrostatic signal of low signal-to-noise ratio based on IMFs optimized reconstruction and wavelet threshold

Relativistic Fock-space multireference coupled cluster theory with full iterative triples for the one-, two-, and three-hole sectors

The relativistic Fock-space coupled cluster method with full iterative inclusion of connected triple excitations (FS-CCSDT) for the 1h0p, 2h0p, and 3h0p Fock space sectors was presented and implemented. The newly developed methods were benchmarked in a series of calculations of both atomic (Ar1/2/3+, I0/1/2+) and molecular (Ar2+, HI+, HI2+) systems for which high-quality experimental data are available. Typical uncertainties in ionization potential and adiabatic excitation energy calculations for FS-CCSD and FS-CCSDT in the low sectors (1h0p and 2h0p) are ∼0.05–0.10 and 0.005–0.02 eV, respectively. The accuracy of the FS-CCSD model is quite similar to that of the relativistic third-order algebraic diagrammatic construction and the closely related equation-of-motion IP-EOM-CCSD and DIP-EOM-CCSD methods. The newly developed relativistic FS-CCSDT model is ∼3 to 5 times more accurate in these sectors. Models formulated for the 3h0p sector provide an acceptable accuracy in calculations of excitation energies of the Ar3+ and I2+ ions with average errors not exceeding 0.13 and 0.06 eV for FS-CCSD and FS-CCSDT, respectively.

AP-1 elements in the promoter and second intron mediate endoplasmic reticulum stress-induced expression of the GPAT3 gene

Abstract An excessive accumulation of hepatic lipids is a characteristic feature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction-associated steatohepatitis (MASH). Acyl-CoA:glycerol-sn-3-phosphate acyltransferase 3 (GPAT3) and other members of the GPAT family are enzymes which play an important role in glycerolipid synthesis. Previous articles have reported that GPAT3 mRNA and ER stress marker genes are upregulated in patients with MASH. Here, we study the regulatory mechanism of GPAT3 gene expression in human hepatoma cells suffering from ER stress. Transcriptome profiling showed that among the genes implicated in the formation of glycerolipids, GPAT3 is one of the most strongly activated genes in response to tunicamycin, an inducer of ER stress. CRISPR/Cas9-mediated disruption of activating transcription factor 4 ( ATF4 ) resulted in reduced GPAT3 expression under ER stress. Luciferase reporter assays of GPAT3 gene fragments encompassing ATF4 ChIP-seq peaks and mutational analysis revealed that activator protein-1 (AP-1) sites located in GPAT3 promoter and intron 2 mediate the activation of transcription in response to ER stress and ATF4. CRISPR/Cas9-mediated deletion of the region containing AP-1 sites from GPAT3 intron 2 caused a reduction of GPAT3 expression and triglyceride content in both unstressed cells and under ER stress. Thus, the results indicate that the induction of GPAT3 expression in response to ER stress is mediated by ATF4 via AP-1 elements in the promoter and second intron.

How accurate are DFT forces? Unexpectedly large uncertainties in molecular datasets

Training of general-purpose machine learning interatomic potentials (MLIPs) relies on large datasets with properties usually computed with density functional theory (DFT). A prerequisite for accurate MLIPs is that the DFT data are well converged to minimize numerical errors. A possible symptom of errors in DFT force components is nonzero net force. Here, we consider net forces in datasets including SPICE, Transition1x, ANI-1x, ANI-1xbb, AIMNet2, QCML, and OMol25. Several of these datasets suffer from significant nonzero DFT net forces. We also quantify individual force component errors by comparison to recomputed forces using more reliable DFT settings at the same level of theory, and we find significant discrepancies in force components averaging from 1.7 meV/Å in the SPICE dataset to 33.2 meV/Å in the ANI-1x dataset. These findings underscore the importance of well converged DFT data as increasingly accurate MLIP architectures become available.

Feeding Drosophila highly radioresistant fungi improves survival and gut morphology following acute gamma radiation exposure

Abstract Diverse fungi have been historically vital reservoirs of drug discovery, providing life-saving pharmaceuticals. Many species of fungi, yeasts in particular, are highly resistant to radiation, with their cellular contents potentially conferring dietary radioresistance. We developed a Drosophila model to test whether feeding two highly radioresistant fungi, Aureobasidium pullulans and Rhodotorula taiwanensis, could improve fly lifespan and gut morphology after acute irradiation. We constructed a dosimetry curve for the lifespan response of males and females to irradiation and found dose-dependent and sex-specific effects on lifespan. We also determined that the sex-specific response to irradiation correlated with nuclear morphology defects in the gut, with the more radiosensitive males displaying increased midgut cellular holes and aberrant nuclear morphology. To determine if feeding Aureobasidium pullulans and Rhodotorula taiwanensis before irradiation could improve survival and gut morphology, we first exclusively fed males and females each fungus and observed that they tolerated the diet well. Using these methods, we found that only two days of pre-feeding Aureobasidium pullulans increased male lifespan, but not female, after irradiation, and improved nuclear morphology in the gut. However, dietary Rhodotorula taiwanensis was not protective. Overall, this study identified a highly radioresistant dietary fungus, Aureobasidium pullulans , as effective for extending male Drosophila lifespan and improving gut morphology following irradiation. Since the gut is particularly sensitive to the effects of irradiation, this fungus indicates a potential therapeutic for patients undergoing radiotherapy. Furthermore, this method could identify additional radioresistant fungi that protect the gut from radiation injury.

Electron transfer controlled by hydrogen bond donor/acceptor exchange in [H2O]6−

We present results from Path Integral Molecular Dynamics simulations that describe the characteristics of the exchange between the hydrogen-bond donor/acceptor roles of two key water molecules in the most stable isomer of the H2O6−, at cryogenic conditions. We investigated a reactive path described in terms of geared rotations of the water pair, which leads to a substantial reorganization of the localization of the excess negative charge. In the reactant and product states, the electron exhibits a surface solvation structure, lying in the vicinity of the acceptor partner of the pair involved in the HB exchange and spanning a spatial domain on the order of 10 Å, away from the cluster boundaries. In contrast, at transition states, the excess charge extends along a spatial realm that encompasses the locations of both partners in the dimer unit, which participate in the electron solvation on an equal footing. The introduction of quantum fluctuations in the treatment of the nuclear coordinates promotes important modifications in the otherwise classical double-well free-energy profile associated with the exchange. The most relevant changes manifest in the appearance of a plateau-like transition-state regime, which is clearly associated with the onset of proton tunneling. Differences in the activation energies between the isolated neutral dimer case and the anionic water hexamer are discussed. The quantum description of the nuclei also promotes a reduction in the predicted vertical detachment energies at reactant/product states; this result contrasts with the increment observed at transition states. In addition, tunneling effects are also manifested in the modifications operative in the electron delocalization at transition states.

Glycopolymer binds pathogenic IgM autoantibodies and pulls them into the mononuclear phagocyte system for degradation

Visualization of hydrogen isotope exchange in single molecule by tip-enhanced Raman images

Intramolecular hydrogen isotope exchange (HIE) plays a pivotal role in regulating molecular photoelectric properties, reaction pathways, and kinetic control. However, due to intrinsic limitations of conventional techniques, direct real-space observation of the atom-by-atom HIE process at the single-molecule level remains challenging, as does the difficulty of accurately counting and locating intramolecular isotope-substituted atoms. Herein, taking the experimentally accessible coronene as a model system, we theoretically demonstrate the capability of tip-enhanced Raman scattering (TERS), modulated by vibrational interference between atomic motions in a given normal mode, to distinguish and identify various hydrogen-to-deuterium isotope substitution configurations. By overlaying mode-specific TERS images at characteristic vibrational frequencies, our approach allows precise determination of the number, spatial positions, and isotopic categories (deuterium/tritium) of exchanged atoms in an individual molecule. These findings establish TERS imaging as a powerful technique to directly visualize intramolecular isotopic transformations, providing new insights into quantum vibrational dynamics and interference-mediated reaction pathways at the nanoscale.

Sleep disorders in renal patients: a comparative analysis of dialysis and post-renal transplant outcomes

Surface hopping with nuclear quantum effects through path-integral coarse graining

Incorporating nuclear quantum effects (NQEs), such as tunneling and zero-point energy, in nonadiabatic dynamics is of fundamental importance. We propose a simple and robust scheme based on introducing an effective quantum potential for the nuclei in mixed quantum-classical trajectory approaches. The most straightforward method is to combine the fewest-switches surface hopping (FSSH) method with centroid molecular dynamics, which we name as centroid-surface surface hopping. Furthermore, the unfavorable computational overhead of path-integral simulations can be mitigated via the recently developed path-integral coarse-graining scheme, achieving efficiency comparable to FSSH with classical nuclei. The method is benchmarked against exact quantum mechanical calculations on two one-dimensional two-state model systems, each with three sets of parameters covering both the golden-rule and near-adiabatic regimes. Results show that our method predicts quantitatively accurate reaction rates and correlation functions, even in the deep tunneling regime, on both model systems for all the parameter sets tested. This development paves the way for efficient and accurate modeling of NQEs in nonadiabatic reactions/processes in the future.

Pemetrexed negatively impacts embryonic development by inducing oxidative stress in mouse oocytes

<i>Ab initio</i> simulations of dynamics of EMI-BF4 ionic liquid propellant used in electrospray thrusters for nanosatellite applications

Detailed quantum-chemistry calculations of field-induced fragmentation reactions of ionic liquids are presented. The simulations identified the most likely channels for hard (breaking covalent bonds) fragmentation. The computed energetics for hard and soft (breaking clusters into moieties) fragmentation can be incorporated in multiscale models of thrusters’ operation. The simulations determined that soft fragmentation occurs on a picosecond timescale, revealing that these large and flexible ions can be heated when accelerated by the electric field. Although the acquired internal kinetic energy is not sufficient to break covalent bonds in cold molecules, it can result in the fragmentation of hotter molecules. The results contribute to a better understanding of processes occurring in thrusters that use ionic liquids as propellants and suggest that deviations from the idealized behavior of the propellant (as charged point-mass particles) in the acceleration region might be important. The results of this study provide a foundation for further improvement of multi-scale models of thrusters’ operation.