Decarboxylation efficiency of carboxylic acids as ligands of metal oxide nanocluster resists upon γ-ray irradiation

Metal oxide nanocluster resists have recently attracted considerable attention for use in extreme ultraviolet (EUV) lithography. To obtain sophisticated guidelines for material design, it is necessary to understand well the radiation-induced chemical reaction scheme including the insolubilization mechanism. In this study, the production of CO2, which is considered to be one of the end products of treatment with an ionizing radiation, was investigated for eight types of carboxylic acid under various conditions using -rays (60Co) as a radiation source. The amount of CO2 produced was measured by gas chromatography (GC). GCO2 (/100 eV), which indicates decarboxylation efficiency, was evaluated. CO2 was generated through electron addition, hole transfer, and hydroxyl radical addition to the molecular and ionic forms of carboxylic acids. The dependences of GCO2 on reaction partners were clarified. The dependences of GCO2 on the molecular structure and dissociative state of carboxylic acids were also clarified.

Sustainable Biodiesel Production by Transesterification of Waste Cooking Oil and Recycling of Wastewater Rich in Glycerol as a Feed to Microalgae

The amount of solid and liquid organic waste and wastewater is continuously increasing all over the world. The necessity of their reuse and recycling is, therefore, becoming more and more pressing. Furthermore, the limited fossil fuel resources, in conjunction with the need to reduce greenhouse gas emissions, advocate the production of renewable fuels. In this work, we analyze a sustainable second-generation process to produce biodiesel by transesterification of waste cooking oil, coupled with a third-generation process in cascade for recycling the incoming wastewater. Since this latter is rich in glycerol, it is used as a feed for microalgae, from which oil can be extracted and added to the waste cooking oil to further produce biodiesel and close the cycle. We studied the influence of different factors like temperature, catalyst load, and reactants ratio on the kinetics of transesterification of the waste oil and estimated the kinetic parameters by different kinetic schemes. The obtained values of activation energies and pre-exponential factors at chosen conditions of T = 60 °C and catalyst load of 0.6% w/w in methanol are: Ea,direct = 35,661 J mol−1, Ea,reverse = 72,989 J mol−1, k0,direct = 9.7708 [dm3 mol−1]3 min−1, and k0,reverse = 24,810 [dm3 mol−1]3 min−1 for the global fourth-order reversible reaction scheme and Ea = 67,348 J mol−1 and k0 = 2.157 × 109 min−1 for the simplified pseudo-first-order irreversible reaction scheme; both in strong agreement with literature data. Furthermore, we designed very efficient conditions for discontinuous and continuous operating mode, both at lab-scale and pilot-scale. The quality of the biodiesel produced from waste cooking sunflower oil is compared with that of biodiesel produced by different kinds of virgin vegetable oils, showing that the former possesses acceptable quality standards (Cetane number = 48 and LHV = 36,600 kJ kg−1). Finally, the recycling of wastewater rich in glycerol as a nutrient for mixotrophic microalgae nurturing is discussed, and microalgae growing kinetics are evaluated (k1 about 0.5 day−1), endorsing the possibility of algae extraction each 4–5 days in a semi-continuous operating mode. The experimental results at the pilot scale finally confirm the quality of biodiesel, and the obtained yields for a two-stage process prove the competitiveness of this sustainable process on the global market.

Demonstration of Equivalence of Generic Glatiramer Acetate and Copaxone®

The objective of the current work was to demonstrate the equivalence of Mylan’s glatiramer acetate (GA) to that of the reference product Copaxone® (COP) using the four criteria for active pharmaceutical ingredient sameness as established by the US Food and Drug Administration (FDA). The reaction scheme used to produce Mylan’s glatiramer acetate (MGA) was compared with that of COP, determined from publicly available literature. Comparative analyses of MGA and COP were performed for physicochemical properties such as amino acid composition and molecular weight distributions. Spectroscopic fingerprints were obtained using circular dichroism spectroscopy. Structural signatures for polymerization and depolymerization including total diethylamine (DEA) content, relative proportions of DEA-adducted amino acids, and N-and C-terminal amino acid sequences were probed with an array of highly sensitive analytical methods. Biological activity of the products was assessed using validated murine Experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. MGA is produced using the same fundamental reaction scheme as COP and was shown to have equivalent physicochemical properties and composition. Analyses of multiple structural signatures demonstrated equivalence of MGA and COP with regard to polymerization, depolymerization, and propagational shift. Examination of the impact on prevention and treatment of EAE demonstrated equivalence of MGA and COP with respect to both activity and toxicity, and thereby provided confirmatory evidence of sameness. A rigorous, multi-pronged comparison of MGA and COP produced using an equivalent fundamental reaction scheme demonstrated equivalent physicochemical properties, structural signatures for polymerization and depolymerization, and biological activity as evidenced by comparable effects in EAE. These studies demonstrate the equivalence of MGA and COP, establishing active ingredient sameness by the US Food and Drug Administration (FDA) criteria for GA, and provide compelling evidence that the FDA-approved generic MGA can be substituted for COP for the treatment of patients with relapsing-remitting MS.

Kinetic Modeling for the “One-Pot” Hydrogenolysis of Cellulose to Glycols over Ru@Fe3O4/Polymer Catalyst

Despite numerous works devoted to the cellulose hydrogenolysis process, only some of them describe reaction kinetics. This is explained by the complexity of the process and the simultaneous behavior of different reactions. In this work, we present the results of the kinetic study of glucose hydrogenolysis into ethylene- and propylene glycols in the presence of Ru@Fe3O4/HPS catalyst as a part of the process of catalytic conversion of cellulose into glycols. The structure of the Ru-containing magnetically separable Ru@Fe3O4/HPS catalysts supported on the polymeric matrix of hypercrosslinked polystyrene was studied to propose the reaction scheme. As a result of this study, a formal description of the glucose hydrogenolysis process into glycols was performed. Based on the data obtained, the mathematical model of the glucose hydrogenolysis kinetics in the presence of Ru@Fe3O4/HPS was developed and the parameter estimation was carried out. The synthesized catalyst was found to be characterized by the enhanced magnetic properties and higher catalytic activity in comparison with previously developed catalytic systems (i.e., on the base of SiO2). The summarized selectivity towards the glycols formation was found to be ca. 42% at 100% of the cellulose conversion in the presence of Ru@Fe3O4/HPS.

Slow conformational changes of blue light sensor BLUF proteins in milliseconds

BLUF (blue light sensor using flavin) proteins consist of flavin-binding BLUF domains and functional domains. Upon blue light excitation, the hydrogen bond network around the flavin chromophore changes, and the absorption spectrum in the visible region exhibits red-shift. Ultimately, the light information received in the BLUF domain is transmitted to the functional region. It has been believed that this red-shift is complete within nanoseconds. Contrary to this commonly accepted scheme, in this study, slow reaction kinetics were discovered in milliseconds (τ1- and τ2-phase) for all the BLUF proteins examined (AppA, OaPAC, BlrP1, YcgF, PapB, SyPixD, and TePixD). Despite extensive reports on BLUF, this is the first clear observation of the BLUF protein absorption change with the duration in the millisecond time region. From the measurements of some domain-deleted mutants of OaPAC and two chimeric mutants of PixD proteins, it was found that the slower dynamics (τ2-phase) are strongly affected by the size and nature of the C-terminal region adjacent to the BLUF domain. Hence, this millisecond reaction is a significant indicator of conformational changes in the C-terminal region, which is essential for the biological functions. On the other hand, the τ1-phase commonly exists in all BLUF proteins, including any mutants. The origin of the slow dynamics was studied using site-specific mutants. These results clearly show the importance of Trp in the BLUF domain. Based on this, a reaction scheme for the BLUF reaction is proposed.

Molecular mechanism of glycolytic flux control intrinsic to human phosphoglycerate kinase

Glycolysis plays a fundamental role in energy production and metabolic homeostasis. The intracellular [adenosine triphosphate]/[adenosine diphosphate] ([ATP]/[ADP]) ratio controls glycolytic flux; however, the regulatory mechanism underlying reactions catalyzed by individual glycolytic enzymes enabling flux adaptation remains incompletely understood. Phosphoglycerate kinase (PGK) catalyzes the reversible phosphotransfer reaction, which directly produces ATP in a near-equilibrium step of glycolysis. Despite extensive studies on the transcriptional regulation of PGK expression, the mechanism in response to changes in the [ATP]/[ADP] ratio remains obscure. Here, we report a protein-level regulation of human PGK (hPGK) by utilizing the switching ligand-binding cooperativities between adenine nucleotides and 3-phosphoglycerate (3PG). This was revealed by nuclear magnetic resonance (NMR) spectroscopy at physiological salt concentrations. MgADP and 3PG bind to hPGK with negative cooperativity, whereas MgAMPPNP (a nonhydrolyzable ATP analog) and 3PG bind to hPGK with positive cooperativity. These opposite cooperativities enable a shift between different ligand-bound states depending on the intracellular [ATP]/[ADP] ratio. Based on these findings, we present an atomic-scale description of the reaction scheme for hPGK under physiological conditions. Our results indicate that hPGK intrinsically modulates its function via ligand-binding cooperativities that are finely tuned to respond to changes in the [ATP]/[ADP] ratio. The alteration of ligand-binding cooperativities could be one of the self-regulatory mechanisms for enzymes in bidirectional pathways, which enables rapid adaptation to changes in the intracellular environment.

The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

Solifenacin (Vesicare®, SOL), known to be a member of isoquinolines, is a muscarinic antagonist that has anticholinergic effect, and it has been beneficial in treating urinary incontinence and neurogenic detrusor overactivity. However, the information regarding the effects of SOL on membrane ionic currents is largely uncertain, despite its clinically wide use in patients with those disorders. In this study, the whole-cell current recordings revealed that upon membrane depolarization in pituitary GH3 cells, the exposure to SOL concentration-dependently increased the amplitude of M-type K+ current (IK(M)) with effective EC50 value of 0.34 μM. The activation time constant of IK(M) was concurrently shortened in the SOL presence, hence yielding the KD value of 0.55 μM based on minimal reaction scheme. As cells were exposed to SOL, the steady-state activation curve of IK(M) was shifted along the voltage axis to the left with no change in the gating charge of the current. Upon an isosceles-triangular ramp pulse, the hysteretic area of IK(M) was increased by adding SOL. As cells were continually exposed to SOL, further application of acetylcholine (1 μM) failed to modify SOL-stimulated IK(M); however, subsequent addition of thyrotropin releasing hormone (TRH, 1 μM) was able to counteract SOL-induced increase in IK(M) amplitude. In cell-attached single-channel current recordings, bath addition of SOL led to an increase in the activity of M-type K+ (KM) channels with no change in the single channel conductance; the mean open time of the channel became lengthened. In whole-cell current-clamp recordings, the SOL application reduced the firing of action potentials (APs) in GH3 cells; however, either subsequent addition of TRH or linopirdine was able to reverse SOL-mediated decrease in AP firing. In hippocampal mHippoE-14 neurons, the IK(M) was also stimulated by adding SOL. Altogether, findings from this study disclosed for the first time the effectiveness of SOL in interacting with KM channels and hence in stimulating IK(M) in electrically excitable cells, and this noticeable action appears to be independent of its antagonistic activity on the canonical binding to muscarinic receptors expressed in GH3 or mHippoE-14 cells.

Transition Metal-Ions Incorporated PEG300 and TDI Based Hydroxy-Terminated Polyurethanes

Present work reports the synthesis of polyethylene glycol, PEG 300 (soft segment) and toluene 2,4-diisocyanate, TDI (hard segment) based hydroxy-terminated polyurethane ligands (HTPU300) for the first time to the best of our knowledge. The effect of 3d transition metal ions with different 3d electrons within HTPU (M(II)-HTPU300, M= Mn, Co, Ni, and Zn) was evaluated by their physical and antibacterial studies of the final complex polymeric unit. M(II) HTPU300 and was conveniently synthesized in appreciable yields following a facile and one-pot addition polymerization reaction scheme. Foremost the thermal stability of all the M(II)-HTPU300 polymeric materials were evaluated using TGA, DSC, and IPDT calculations. FTIR technique was used to ascertain the structure of M(II)-HTPU300, while SEM/EDX and XRD techniques were used to study their morphology, elemental analysis, and crystalline nature of the material, respectively. Further, the in-vitro antimicrobial activity of the PU was investigated against gram-positive (Staphylococcus aureus, Bacillus subtilis) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. The comparatively moderate efficacy against bacterial stain supports the possible application of such PU as thermally stable bacterial resistant materials constructed out of degradable PEG.

Dimensional control over metal halide perovskite crystallization guided by active learning

Metal halide perovskite (MHP) derivatives, a promising class of optoelectronic materials, have been synthesized with a range of dimensionalities that govern their optoelectronic properties and determine their applications. We demonstrate a data-driven approach combining active learning and high-throughput experimentation to discover, control, and understand the formation of phases with different dimensionalities in the morpholinium (morph) lead iodide system. Using a robot-assisted workflow, we synthesized and characterized two novel MHP derivatives that have distinct optical properties: a one-dimensional (1D) morphPbI3 phase ([C4H10NO][PbI3]) and a 2D (morph)2PbI4 phase ([C4H10NO]2[PbI4]). To efficiently acquire the data needed to construct a machine learning (ML) model of the reaction conditions where the 1D and 2D phases are formed, data acquisition was guided by a diverse-mini-batch-sampling active learning algorithm, using prediction confidence as a stopping criterion. Querying the ML model uncovered the reaction parameters that have the most significant effects on dimensionality control. Based on these insights, we propose a reaction scheme that rationalizes the formation of different dimensional MHP derivatives in the morph-Pb-I system. The data-driven approach presented here, including the use of additives to manipulate dimensionality, will be valuable for controlling the crystallization of a range of materials over large reaction-composition spaces.

Microwave Synthesis of Magnetite Nanoparticles and Mg-Doped Magnetite Nanoparticles by Precipitation of Fe2+ Ions

This study is focused on a simple and fast synthesis of nonstoichiometric magnetite nanoparticles with the chemical formula Fe3−XO4 and magnesium ferrite nanoparticles (Mg1−XFe2+XO4). The nanoparticles were prepared with Fe2+ ions (FeSO4 · H2O) alkalised by KOH under oxidative conditions and in a microwave field. X-ray powder diffraction (XRD) and 57Fe transmission Mössbauer spectroscopy were used to determine the phase composition and crystal structure in detail. The presence of synthetic magnetite, maghemite, goethite, and magnesium ferrite was observed. Room temperature Mössbauer spectroscopy revealed the existence of ferromagnetic sublattices and superparamagnetic fraction. The superparamagnetic component corresponds to magnesium ferrite nanoparticles. Low temperature Mössbauer spectroscopy was used to locate the blocking temperature of superparamagnetic nanoparticles and to separate the sublattices. The presumed spherical morphology of nanoparticles and their size under 100 nm have been confirmed by transmission electron microscopy (TEM). The obtained results were used to provide possible reaction scheme, which serves to tailor the synthesis to a desired application.