The Influence of Oxidant on Gelatin–Tannin Hydrogel Properties and Structure for Potential Biomedical Application

Nowadays, there is a widespread usage of sodium periodate as an oxidant for synthesizing gelatin–tannin hydrogels. The impact of iodine compounds could have a harmful effect on human health. The study focuses on the proposal of alternative oxidizing systems for tannin oxidation. Gelatin–tannin hydrogels were obtained based on the usage of H2O2/DMSO/KMnO4/KIO4 oxidants and characterized with sorption, thermal (TGA, DTG, DSC), mechanical, FTIR and other methods. The sorption experiments were carried out in a phosphate buffer (pH = 5.8/7.4/9) and distilled water and were investigated with Fick’s law and pseudosecond order equation. The pH dependence of materials in acid media indicates the possibility of further usage as stimuli-responsive systems for drug delivery. Thermal transitions demonstrate the variation of structure with melting (306 ÷ 319 °C) and glass transition temperatures (261 ÷ 301 °C). The activation energy of water evaporation was calculated by isoconversional methods (Kissinger–Akahira–Sunose, Flynn–Wall–Ozawa) ranging from 4 ÷ 18 to 14 ÷ 38 kJ/mole and model-fitting (Coats–Redfern, Kennedy–Clark) methods at 24.7 ÷ 45.3 kJ/mole, indicating the smooth growth of values with extent of conversion. The network parameters of the hydrogels were established by modified Flory–Rehner and rubber elasticity theories, which demonstrated differences in values (5.96 ÷ 21.27·10−3 mol/cm3), suggesting the limitations of theories. The sorption capacity, tensile strength and permeability for water/oxygen indicate that these materials may find their application in field of biomaterials.

Explicit-pH Coarse-Grained Molecular Dynamics Simulations Enable Insights into Restructuring of Intestinal Colloidal Aggregates with Permeation Enhancers

Permeation enhancers (PEs) can increase the bioavailability of drugs. The mechanisms of action of these PEs are complex, but, typically, when used for oral administration, they can transiently induce the alteration of trans- and paracellular pathways, including increased solubilization and membrane fluidity, or the opening of the tight junctions. To elucidate these mechanistic details, it is important to understand the aggregation behavior of not only the PEs themselves but also other molecules already present in the intestine. Aggregation processes depend critically on, among other factors, the charge state of ionizable chemical groups, which is affected by the pH of the system. In this study, we used explicit-pH coarse-grained molecular dynamics simulations to investigate the aggregation behavior and pH dependence of two commonly used PEs—caprate and SNAC—together with other components of fasted- and fed-state simulated intestinal fluids. We also present and validate a coarse-grained molecular topology for the bile salt taurocholate suitable for the Martini3 force-field. Our results indicate an increase in the number of free molecules as a function of the system pH and for each combination of FaSSIF/FeSSIF and PEs. In addition, there are differences between caprate and SNAC, which are rationalized based on their different molecular structures and critical micelle concentrations.

Review of the Hydrogen Evolution Reaction—A Basic Approach

An increasing emphasis on energy storage resulted in a surge of R&D efforts into producing catalyst materials for the hydrogen evolution reaction (HER) with emphasis on decreasing the usage of platinum group metal (PGMs). Alkaline water electrolysis holds promise for satisfying future energy storage demands, however the intrinsic potential of this technology is impeded by sluggish reaction kinetics. Here, we summarize the latest efforts within alkaline HER electrocatalyst design, where these efforts are divided between three catalyst design strategies inspired by the three prevailing theories describing the pH-dependence of the HER activity. Modifying the electronic structure of a host through codoping and creating specific sites for hydrogen/hydroxide adsorption stand out as promising strategies. However, with the vast amount of possible combinations, emphasis on screening parameters is important. The authors predict that creating a codoped catalyst using the first strategy by screening materials based on their hydrogen, hydroxide and water binding energies, and utilizing the second and third strategies as optimization parameters might yield both active and stable HER catalyst materials. This strategy has the potential to greatly advance the current status of alkaline water electrolysis as an energy storage option.

Relationship between monomer packing and receptor binding domain pocket status in the spike trimer of SARS-CoV-2 variants

Existence of a SARS-CoV-2 spike protein trimer form with closer packing between monomers when receptor binding domains (RBDs) are all down, locked as opposed to closed, has been associated with linoleic acid (LA) binding at neutral pH, or can occur at acidic pH in the absence of LA binding. The relationship between degree of closure of the LA binding pocket of the RBD, and monomer burial in the trimer, is examined for a range of spike protein structures, including those with D614G mutation, and that of the Delta variant (which also carries D614G). Some spike protein structures with this aspartic acid mutation show monomer packing approaching that of the locked form (at neutral pH, without LA binding) for two segments, a third (around the RBD) remains less closely packed. Analysis of other coronavirus RBD structures suggests that mutation of the RBD in spike protein of the Omicron variant could lead to LA binding pocket changes. It is proposed that these changes could lead to one of two consequences for the Omicron variant spike protein (which also has the D614G mutation), at neutral pH and without LA binding, either easier access to a locked form throughout that leads to cooperative transitions between all RBD down and all RBD up, or maintenance of a spike trimer with locked characteristics C-terminal to the RBD at the same time as the RBD is free to transit between down and up states. The situation may also be impacted by spike protein charge mutations in the Omicron lineage that alter pH-dependence around the RBD, in a similar way to the changes induced elsewhere by D614G.

Using pH dependence to understand mechanisms in electrochemical CO reduction

Electrochemical conversion of CO(2) into hydrocarbons and oxygenates is envisioned as a promising path towards closing the carbon cycle in modern technology. To this day, however, the reaction mechanisms towards the plethora of products are disputed, complicating the search for novel catalyst materials. In order to conclusively identify the rate-limiting steps in CO reduction on Cu, we analyzed the mechanisms on the basis of constant potential DFT kinetics and experiments at a wide range of pH values (3 - 13). We find that *CO dimerization is energetically favoured as the rate limiting step towards multi-carbon products. This finding is consistent with our experiments, where the reaction rate is nearly unchanged on an SHE potential scale, even under acidic conditions. For methane, both theory and experiments indicate a change in the rate-limiting step with electrolyte pH from the first protonation step in acidic/neutral conditions to a later one in alkaline conditions. We also show, through a detailed analysis of the microkinetics, that a surface combination of *CO and *H is inconsistent with the measured current densities and Tafel slopes. Finally, we discuss the implications of our understanding for future mechanistic studies and catalyst design.

Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs

β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (βCDLip) or galactosamine (βCDGAL), were significantly larger than that of the native βCD. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with βCDLip and βCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications.

Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 Cl−/H+ Antiporter

Intracellular transport of chloride by members of the CLC transporter family involves a coupled exchange between a Cl− anion and a proton (H+), which makes the transport function dependent on ambient pH. Transport activity peaks at pH 4.5 and stalls at neutral pH. However, a structure of the WT protein at acidic pH is not available, making it difficult to assess the global conformational rearrangements that support a pH-dependent gating mechanism. To enable modeling of the CLC-ec1 dimer at acidic pH, we have applied molecular dynamics simulations (MD) featuring a new force field modification scheme—termed an Equilibrium constant pH approach (ECpH). The ECpH method utilizes linear interpolation between the force field parameters of protonated and deprotonated states of titratable residues to achieve a representation of pH-dependence in a narrow range of physiological pH values. Simulations of the CLC-ec1 dimer at neutral and acidic pH comparing ECpH-MD to canonical MD, in which the pH-dependent protonation is represented by a binary scheme, substantiates the better agreement of the conformational changes and the final model with experimental data from NMR, cross-link and AFM studies, and reveals structural elements that support the gate-opening at pH 4.5, including the key glutamates Gluin and Gluex.