Combination disease-modifying treatment in spinal muscular atrophy: A proposed classification

We sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA

Theoretical evaluation of the antioxidant activity of some stilbenes using the Density Functional Theory

In this paper, the antiradical potential of trans-2,4,3′,5′-tetrahydroxystilbene (T-OXY), trans-2,3′,4-trihydroxystilbene (T-RES), cis-2,4,1′,3′-tetrahydroxystilbene (C-OXY) and cis-2,1′,4-trihydroxystilbene (C-RES) is investigated by BDE (E0) and ETS-NOCV calculations, in water, benzene, DMSO, and ethanol. The study of solubility by the COSMO-RS model demonstrates that the compounds are very soluble in DMSO. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms are explored as possible oxidation paths of these compounds using the DFT calculations at B3LYP/6-311++G(2d,2p) level of theory in DMSO. For all the studied compounds, the HAT was found to be the thermodynamically dominant mechanism, indicating that the investigated compounds can be classified according to their antiradical activity in the following sequence order T-OXY˃T-RES˃C-OXY˃C-RES. The evaluation of ΔHBDE reaction enthalpies, ΔHIP, and ΔHPA linked to the three mechanisms with certain radicals (HO·, HOO·, CH3O· and CH3OO·, NO·, and NO2·) are determined. The results indicate the HAT and SPLET mechanisms are competitive in inhibiting those species. QTAIM calculations reveal the existence of critical points in the two conformers. The Diels-Alder intramolecular cyclization of (C-OXY) leads to two new tautomers: trans-cycle-OXY (T-CYCLE-OXY) and cis-cycle-OXY (C-CYCLE-OXY) with a significant improvement in the antioxidant activity. In conclusion, T-OXY and T-CYCLE-OXY are identified as the best antioxidant candidates among those tested

Clorazepate removal from aqueous solution by adsorption onto maghnite: Experimental and theoretical analysis

The removal of a benzodiazepine (clorazepate, CLZ) from aqueous solution by adsorption onto maghnite clay is investigated supported by theoretical simulations. The Fourier-transform infrared (FTIR), Ultraviolet (UV), X-ray diffraction (XRD), and scanning electron microscope (SEM) analyses were used to characterize the adsorbent. To individuate the optimum conditions for adsorption, equilibrium, and kinetic tests are performed to assess the efficiency of this adsorbent to remove CLZ from polluted water in different operating conditions like pH, initial concentration, adsorbent dosage, and contact time. Adsorption is maximum at low pH, and it is mainly driven by electrostatic interactions between the benzenic ring of CLZ molecule and the montmorillonite layer of maghnite adsorbent. The kinetics obeys to the pseudo-first-order kinetic model, while the Freundlich isotherm model was found to better describe the adsorption equilibrium. The maximum observed adsorption amount of CLZ onto maghnite was about 50 mg g−1 at pH 4.66. A complementary theoretical study is performed to quantify the CLZ/maghnite interactions using Monte Carlo simulations. Interestingly, the results show that the CLZ assumes a horizontal position on the maghnite surface upon adsorption, characterized by high energy adsorption

Preparation, characterization and dye adsorption properties of activated olive residue and their novel bio-composite beads: New computational interpretation

Preparation, characterization, and application of activated olive residue (ROA) and their novel biocompatible bio-composite beads (ROA/AS) are investigated. The adsorbents are characterized by FTIR, XRD, and SEM and subsequently tested to remove methylene blue (MB) taken as a probe-pollutant. Experimental results show a marked enhancement in the adsorptive removal of MB by ROA/AS bio-composite beads as compared to ROA. When statistical physics theory is used to describe the dye removal process, the best match for experimental adsorption isotherms is a monolayer isotherm model coupled with real gas law (MMRG model). Quantum chemical descriptors including frontier orbital energies (EHOMO and ELUMO), gap energy (ΔE), dipole moment (μ), and Fukui index have also been computed and discussed. All the examined systems' adsorption and interaction energies are estimated using Monte Carlo and molecular dynamics simulations. To summarize, integrated experimental and computational calculations have shown to be unique and robust techniques for in-depth investigations of physical processes such as adsorption, providing crucial insights at the molecular level to elucidate the adsorption mechanism

Molecular modeling of cationic dyes adsorption on agricultural Algerian olive cake waste

International audienceIn this research, the adsorption isotherms of Methylene Blue (MB) and Basic Yellow 28 (BY28) on agricultural Algerian olive cake waste (AAOCW) were modeled at molecular level using statistical physics and COSMO–RS theories. This molecular modeling aimed to demonstrate an alternative way to describe the interactions between dyes and adsorbents. The adsorption equilibrium isotherms of MB and BY28 on AAOCW were constructed at different temperatures. The statistical physics model was used to quantify the number of adsorbed dye molecules per site, the anchorage number, the receptor sites density, the adsorbed quantity at saturation, the concentration at half saturation and the molar adsorption energy. The COSMO–RS theory was used to quantify the interaction energies Electrostatic, hydrogen bonding and Van der Waals. σ–Profile and σ–potential were calculated to show the ability of each of the two dyes to interact with every adsorbent site. It was demonstrated that statistical physics and COSMO–RS theories are confident ways to elucidate the interactions between dye molecules and adsorbent surface at a molecular level. © 2018 Elsevier B.V

Multitask Quantum Study of the Curcumin‐Based Complex Physicochemical and Biological Properties

Density functional theory (DFT), time‐dependent density functional theory (TDDFT), quantum theory of atoms in molecules (QTAIM), and extended transition state natural orbitals for chemical valence (ETS‐NOCV) have all been used to investigate the physicochemical and biological properties of curcumin and three complexes, i.e., Cur‐M (M = Ni, Cu, and Mg). Based on DFT calculations, the enolic form (Cur‐Enol) is more stable than the anti‐diketone form (Cur‐Anti diketone) favored for complexation. This enolic form stability was explained by the presence of three intramolecular hydrogen bonds according to the QTAIM analysis. Furthermore, the ETS‐NOCV technique revealed that the enolic form had more significant antioxidant activity compared with the anti‐diketone form. The calculations from the COnductor‐like Screening MOdel for Realistic Solvents (COSMO‐RS) showed that the dimethyl sulfoxide (DMSO) solvent could dissolve all the curcumin tautomers Cur‐Enol, Cur‐Anti‐diketone and Cur‐Cu, Cur‐Mg, and Cur‐Ni complexes in contrast to benzene, acetone, octanol, ethanol, methanol, and water. Furthermore, except for Cur‐Mg, which had a relatively low solubility (14 g/L), all complexes were insoluble in water. Cur‐Antidiketone was considerably more soluble than Cur‐Enol in the examined solvents

Experimental and detailed DFT/MD simulation of α-aminophosphonates as promising corrosion inhibitor for XC48 carbon steel in HCl environment

Background: Corrosion is a pervasive issue in several industries, causing safety hazards and substantial economic losses. α-aminophosphonate substances have recently garnered attention for their ability to inhibit corrosion. In this study, two specific α-aminophosphonate molecules, namely diethyl(furan-2-yl(phenylamino)methyl) phosphonate (AMP1) and diethyl((2methoxyphenyl) amino) (thiophene-2-methyl) phosphonate (AMP2) were evaluated for their potential as anticorrosion agents for XC48 carbon steel under acidic conditions. Methods: Their corrosion inhibition was examined towards XC48 carbon steel under 1.0 M HCl solution utilizing the electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), atomic force microscope (AFM), scanning electron microscope (SEM), contact angle, Density functional theory (DFT), molecular dynamics (MD), and atoms in molecule (AIM). Significant findings: Results showed that AMP1 and AMP2 had inhibition efficiencies of 83.34% and 63.82% for EIS and 82.70% and 74.57% for PDP, respectively. The inhibition mechanism involved adsorption of the additives onto the metal surface via Langmuir isotherm. The study also demonstrated the influence of temperature on inhibition efficiency, with nearly 70% inhibition observed at 298 to 323 K. AFM and SEM analyses revealed chemisorption coating formation inhibiting acid attack, and contact angle analyses showed the surface to be hydrophobic. Theoretical analyses using DFT, MD, and AIM were used to clarify the inhibitors' adsorption effect on XC48 steel, showing a high agreement with experimental findings