Effect of Local Chain Dynamics on the Structure of Free Volume Elements in Glassy Polymer Membranes from All-Atom Molecular Dynamics Simulations

Polymers are attractive membrane materials owing to their mechanical robustness and relatively inexpensive fabrication. An important dictator of membrane performance are free volume elements (FVEs), microporous void spaces created by the inefficient packing of bulky groups along the polymer chain. FVEs tend to degrade over time as polymer chains reorganize irreversibly; relating local chain dynamics to the distribution of FVEs can help control phenomena like plasticization and aging. In this work, we implement all-atom molecular dynamics (MD) simulations to study three polymers with different glass transition temperatures (Tg): polymethylpentene (PMP), polystyrene (PS), and HAB-6FDA thermally rearranged polymer (TRP). We observe that chain segments near FVEs have higher mobility compared to the atoms in the bulk; the extent of this difference is a function of Tg. To capture penetrant diffusion through the polymer matrix, hydrogen is inserted, and the mean squared displacement is calculated; penetrant mobility is dependent on both FVE distribution and polymer chain dynamics.Comment: 20 pages, supplementary information appended, codes and initial structures available at our GitHub page https://github.com/UFSRG/published-work/tree/main/2022-Otmi-Macroletter

Evolution of Free Volume Elements in Amorphous Polymers Undergoing Uniaxial Deformation: a Molecular Dynamics Simulation Study

Amorphous polymers are considered promising materials for separations due to their excellent transport properties and low fabrication costs. The separation performance of a membrane material is characterized by its permeability (overall throughput of components), and selectivity (efficiency of separation). Both permeability and selectivity are controlled by the diffusion of different penetrants through the matrix, which is strongly influenced by the distribution and morphology of the free volume elements (FVEs). FVEs are void spaces in the polymer matrix that result from the inefficient packing of bulky and rigid groups on the polymer backbone. Thus, FVEs dictate the efficiency of membrane polymers, and it is imperative to understand how processing conditions such as high pressure influence their structure. In this paper, we apply uniaxial tensile deformation on three polymers, namely polystyrene (PS), polymethylpentene (PMP), and HAB-6FDA thermally rearranged polymer (TRP), at varying temperatures and strain rates. We calculate the stress strain curve, tensile modulus, and free volume element evolution at these conditions. We find that PMP and PS with low and moderate glass transition temperature, respectively, exhibit the most change in mechanical properties as a function of strain rate and temperature. The properties of TRP, however, do not vary as much. We also find that FVEs become larger with deformation, and the extent of this change is in line with the overall change of mechanical properties of the material.Comment: Brendan Wernisch and Mohammed Al Otmi contributed equally to this wor

Improvement of Lead Acetate-Induced Testicular Oxidative Damage by Vitis Vinifera (Linn.) Seed Extract In Adult Wistar Rats

Introduction: Lead is the most ubiquitous hazardous toxin in the environment. It’s a severe threat to public health and especially to the male reproductive system. In recent years, the usage of the antioxidant to reduce the toxicity of heavy metals has expanded globally. Antioxidants can prevent or minimise the oxidation of other molecules by ROS in a tissue or cell. Grape seeds are natural, rich sources of antioxidant compounds. Aim/Objective: The present study was undertaken to investigate the effect of GSE (grape seed extract) against lead acetate-induced testicular oxidative damage on testis of Wistar rats. Materials and Methods: 24 male Wistar rats were used in the study. They were split into two groups: Group I was the control group (6 rats), and Group II had 18 rats that were given LA at 50 mg/kg BW for 28 days. On the 28th day, all 18 rats were subdivided into three groups: Group II(a) (LA Cessation), Group II(b), and Group II(c) treated with GSE once a day, orally, up to the 56th day. A preliminary phytochemical analysis was conducted. The testicular weight, enzymatic and non- enzymatic oxidative stress markers were estimated. Results: The phytochemical screening showed that bioactive compounds present in the GSE, including phenols, tannins, flavonoids, anthocyanin, glycosides, triterpenoids, and alkaloids. In addition, there was a significant decrease in SOD, CAT, GPx, and GSH levels and a significantly elevated MDA concentration. However, post-treatment with GSE significantly restored the testicular oxidative damage caused by LA in the testis. Conclusion: We concluded that the GSE may have the potential to provide a promising therapeutic effect against LA-induced testicular toxicity

Molecular Driving Forces in the Self-Association of Silaffin Peptide R5 from MD Simulations

The 19-residue silaffin-R5 peptide has been widely studied for its ability to precipitate uniform SiO2 particles through mild temperature and pH pathways, in the absence of any organic solvents. There is consensus that post-translational modification (PTM) of side chains has a large impact on the biomineralization process. Thus, it is imperative to understand the precise mechanisms that dictate the formation of SiO2 from R5 peptide, including the effects of PTM on peptide aggregation and peptide-surface adsorption. In this work, we use molecular dynamics (MD) simulations to study the aggregation of R5 dimer with multiple PTMs, with the presence of different ions in solution. Since this system has strong interactions with deep metastable states, we use parallel bias metadynamics with partitioned families to efficiently sample the different states of the system. We find that peptide aggregation is a prerequisite for biomineralization. We observe that the electrostatic interactions are essential in the R5 dimer aggregation; for wild type R5 that only has positively charged residues, phosphate ions HPO42- in the solution form a bridge between two peptides and are essential for peptide aggregation. Alternatively, the post translational modification phosphorylation, which renders neutral serine residues negative, enables R5 to aggregate without phosphate ion. The extent of phosphorylation and location of phosphorylated residues on R5 peptide results in different behavior and extent of aggregation - the aggregation trend of R5 peptide that we observe is in line with SiO2 precipitation observed in previous experimental studies, proving that peptide aggregation is a prerequisite for biomineralization

Effect of Tinospora cordifolia on Oxidative Stress Level due to Drug Induced Nephrotoxicity: An Experimental Study

Introduction: Various herbs are known to confer nephroprotectivity against renal damage of different origins. Tinospora cordifolia (Willd.) Miers is known to treat kidney disorders. Yet, a lacuna of studying the protective effect of the herb on drug induced nephrotoxicity at different time periods exists. Aim: To determine the protective effect of T. cordifolia (Willd.) Miers on drug induced nephrotoxic biochemical changes upon post-treatment with the herb. Materials and Methods: An experimental study was carried out at the Centre for Toxicology and Developmental Research, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India, from September 2020 to October 2020. Gentamicin induced drug nephrotoxicity model was employed for the study. The ethanolic extract of T. cordifolia was prepared. Total 51 adult male Wistar rats were housed under standard animal laboratory conditions for 30 days and were assigned to four groups: Control group (Olive oil, per os), Nephrotoxicity group (Gentamicin), Toxicity cessation group (Gentamicin-Olive oil) and Post-treatment group (Gentamicin T. cordifolia ethanolic extract). To induce nephrotoxicity, gentamicin (100 mg/kg) was administered through the Intraperitoneal (IP) route for 8 days. The ethanolic extract of the stem of T. cordifolia (Willd.) Miers (400 mg/kg) was administered orally for one, two and three weeks following nephrotoxicity induction. Levels of activity of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), Reduced Glutathione (GSH) content and Lipid peroxidation in the kidney were measured. Statistical analysis was performed using One-way Analysis of Variance (ANOVA) and Post-hoc tests. Results: The reduction in SOD (6.33±1.19 unit/ mg/mt), CAT (57.56±25.89 mcm/mt/mg ptn), GPx (5.79±1.87 nm/mt/mg ptn) activity, and GSH (4.98±0.31mcm/g tissue) levels and increase in the lipid peroxidation (196.28±100.05 nm/g tissue) in the kidney due to gentamicin nephrotoxicity was reversed upon post-treatment with T. cordifolia (Willd.) Miers extract for 1 week (7.06±0.25 unit/mg/mt, 119.69±22.79 mcm/mt/ mg ptn, 7.08±1.73 nm/mt/mg ptn, 6.19±0.99 mcm/g tissue and 93.10±9.11 nm/g tissue), 2 weeks (7.03±0.43 unit/ mg/ mt, 181.79±39.00 mcm/mt/mg ptn, 5.07±0.81 nm/mt/mg ptn, 7.58±0.73 mcm/g tissue and 188.31±54.89 nm/g tissue) and 3 weeks (7.81±0.47 unit/mg/mt, 165.83±37.48 mcm/mt/ mg ptn, 3.92±1.87 nm/mt/mg ptn, 7.03±1.28 mcm/g tissue, 214.40±72.93 nm/g tissue). Conclusion: Post-treatment with T. cordifolia (Willd.) Miers stem extract is protective in drug induced nephrotoxic condition, even upon 1 week of administration. Its therapeutic influence on the alterations in the oxidative stress markers and antioxidant levels produced due to gentamicin nephrotoxicity has been demonstrate

Solid-State NMR and MD Study of the Structure of the Statherin Mutant SNa15 on Mineral Surfaces

International audienceElucidation of the structure and interactions of proteins at native mineral interfaces is key to understanding how biological systems regulate the formation of hard tissue structures. In addition, understanding how these same proteins interact with non-native mineral surfaces has important implications for the design of medical and dental implants, chromatographic supports, diagnostic tools, and a host of other applications. Here, we combine solid-state NMR spectroscopy, isotherm measurements, and molecular dynamics simulations to study how SNa15, a peptide derived from the hydroxyapatite (HAP) recognition domain of the biomineralization protein statherin, interacts with HAP, silica (SiO 2) and titania (TiO 2) mineral surfaces. Adsorption isotherms are used to characterize the binding affinity of SNa15 to HAP, SiO 2 , and TiO 2. We also apply 1D 13 C CP MAS, 1D 15 N CP MAS, and 2D 13 C-13 C DARR experiments to SNa15 samples with uniformly 13 C-and 15 N-enriched residues to determine backbone and side-chain chemical shifts. Different computational tools, namely TALOS-N and molecular dynamics simulations, are used to deduce secondary structure from backbone and side-chain chemical shift data. Our results show that SNa15 adopts an α-helical conformation when adsorbed to HAP and TiO 2 , but the helix largely unravels upon adsorption to SiO 2. Interactions with HAP are mediated in general by acidic and some basic amino acids, although the specific amino acids involved in direct surface interaction vary with surface. The integrated experimental and computational approach used in this study is able to provide high-resolution insights into adsorption of proteins on interfaces

Studies of dynamic binding of amino acids to TiO2 nanoparticle surfaces by Solution NMR and Molecular Dynamics Simulations

Adsorption of biomolecules onto material surfaces involves a potentially complex mechanism where molecular species interact to varying degrees with a heterogeneous material surface. Surface adsorption studies by atomic force microscopy (AFM), Sum Frequency Generation (SFG) spectroscopy, and solid state NMR (ssNMR), detect the structures and interactions of biomolecular species that are bound to material surfaces and which, in the absence of a solid liquid interface, do not exchange rapidly between surface-bound forms and free molecular species in bulk solution. Solution NMR has the potential to complement these techniques by detecting and studying transiently bound biomolecules at the liquid-solid interface. Herein we show that dark-state exchange saturation transfer (DEST) NMR experiments on gel-stabilized TiO2 nanoparticle (NP) samples detect several forms of biomolecular adsorption onto titanium (IV) oxide surfaces. Specifically, we use the DEST approach to study the interaction of amino acids arginine (Arg), lysine (Lys), leucine (Leu), alanine (Ala), and aspartic acid (Asp) with TiO2 rutile nanoparticle surfaces. Whereas Leu, Ala, and Asp display only a single weakly interacting form in the presence of TiO2 nanoparticles , Arg and Lys displayed at least two distinct bound forms: a species that is surface bound and retains a degree of reorientational motion, and a second more tightly bound form characterized by broadened DEST profiles upon addition of TiO2 nanoparticles. Molecular Dynamics simulations indicate different surface bound states for both Lys and Arg depending on the degree of TiO2 surface hydroxylation, but only a single bound state for Asp regardless of the degree of surface hydroxylation, in agreement with results obtained from analysis of DEST profiles