Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice.

Background: Repurposing dantrolene to treat Alzheimer's disease has been shown to be effective in amyloid transgenic mouse models but has not been examined in a model of tauopathy. Objective: The effects of a nanoparticle intranasal formulation, the Eagle Research Formulation of Ryanodex (ERFR), in young adult and aged wild type and PS19 tau transgenic mice was investigated. Methods: The bioavailability of intranasal ERFR was measured in 2 and 9-11-month-old C57BL/6J mice. Blood and brain samples were collected 20 minutes after a single ERFR dose, and the plasma and brain concentrations were analyzed. Baseline behavior was assessed in untreated PS19 tau transgenic mice at 6 and 9 months of age. PS19 mice were treated with intranasal ERFR, with or without acrolein (to potentiate cognitive dysfunction), for 3 months, beginning at 2 months of age. Animal behavior was examined, including cognition (cued and contextual fear conditioning, y-maze), motor function (rotarod), and olfaction (buried food test). Results: The dantrolene concentration in the blood and brain decreased with age, with the decrease greater in the blood resulting in a higher brain to blood concentration ratio. The behavioral assays showed no significant changes in cognition, olfaction, or motor function in the PS19 mice compared to controls after chronic treatment with intranasal ERFR, even with acrolein. Conclusions: Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice.

Effects of intranasal dantrolene nanoparticles on brain concentration and behavior in PS19 tau transgenic mice.

Background: Repurposing dantrolene as a potential disease-modifying treatment for Alzheimer's disease has been shown to be effective in amyloid transgenic mouse models but has not been examined in a model of tauopathy. Objective: The effects of a nanoparticle intranasal formulation, the Eagle Research Formulation of Ryanodex (ERFR), in young adult and aged wild type and PS19 tau transgenic mice was investigated. Methods: The bioavailability of intranasal ERFR was measured in 2 months and 9-12 month old C57BL/6J male mice. Mice received a single intranasal dose of ERFR and, after 20 min, blood and brain samples were collected. Dantrolene concentrations in the plasma and brain were analyzed by High Performance Liquid Chromatography. Animal behavior was examined in PS19 tau transgenic mice, with/without acrolein treatment to exacerbate cognitive deficits. Behavioral tests included cognition (cued and contextual fear conditioning, y-maze), motor function (rotarod), and olfaction (buried food test). Results: Dantrolene concentration in the blood and brain decreased with age, though the decrease was greater in the blood resulting in a higher brain to blood concentration ratio. The behavioral assays showed no significant changes in cognition, olfaction or motor function in the PS19 mice compared to controls after chronic ERFR treatment even with acrolein treatment. Conclusion: Our studies suggest that while we did not find PS19 mice to be a reliable Alzheimer animal model to test the therapeutic efficacy of dantrolene, the results suggest a potential for ERFR to be an effective chronic therapy for Alzheimer's disease and that further studies are indicated.

Visible-Light-Mediated Three-Component Cascade Sulfonylative Annulation.

Visible-light-promoted cascade radical cyclization for the synthesis of sulfonylated benzimidazo/indolo[2,1-a]iso-quinolin-6(5H)-ones has been reported. The reaction provides transition-metal-free and expeditious access to sulfonylated polyaromatics. The use of sodium metabisulfite as a SO2 surrogate and the rapid generation of molecular complexity using a three-component photochemical protocol are the salient features of this reaction manifold.

Visible-light-mediated synthesis of α,ß-diamino esters via coupling of N,N-dimethylanilines and glyoxalic oxime ethers.

A visible-light-mediated synthesis of α,ß-diamino esters has been developed via the cross coupling of N,N-dimethylanilines with glyoxalic oxime ethers. This protocol involves the generation of α-aminoalkyl radicals under mild reaction conditions, provides α,ß-diamino esters in good to excellent yields, and can be performed on a gram-scale.

Antibacterial and Antiviral Functional Materials: Chemistry and Biological Activity toward Tackling COVID-19-like Pandemics.

The ongoing worldwide pandemic due to COVID-19 has created awareness toward ensuring best practices to avoid the spread of microorganisms. In this regard, the research on creating a surface which destroys or inhibits the adherence of microbial/viral entities has gained renewed interest. Although many research reports are available on the antibacterial materials or coatings, there is a relatively small amount of data available on the use of antiviral materials. However, with more research geared toward this area, new information is being added to the literature every day. The combination of antibacterial and antiviral chemical entities represents a potentially path-breaking intervention to mitigate the spread of disease-causing agents. In this review, we have surveyed antibacterial and antiviral materials of various classes such as small-molecule organics, synthetic and biodegradable polymers, silver, TiO2, and copper-derived chemicals. The surface protection mechanisms of the materials against the pathogen colonies are discussed in detail, which highlights the key differences that could determine the parameters that would govern the future development of advanced antibacterial and antiviral materials and surfaces.

Effect of NiO Precursor Solution Ageing on the Perovskite Film Formation and Their Integration as Hole Transport Material for Perovskite Solar Cells.

Exceptional progress in the performance of perovskite solar cells in a very short time has made it a potential photovoltaic technology for future deployment. The compositional engineering in perovskite materials and other buffer layers makes it a feasible candidate for commercial applications in the near future. However, there are certain challenges associated with these devices which need to be addressed such as device stability, process dependent device efficiency, hole transport layer (HTL) etc. The device performance is highly dependent on the processing parameters of the precursors. Understanding the origin of this challenge is very crucial for reproducible device performance. In this work, we have focused on utilizing NiO as a HTL in planar perovskite solar cells and studied the ageing effect of NiO precursor solution on the perovskite film quality in terms of crystallinity, grain growth, surface morphology, and overall device performance. It is observed that the ageing of NiO precursor promotes the formation of NiO films with increased roughness which improves the perovskite film quality. Structural and morphological studies revealed that the perovskite films formed on aged NiO films were highly crystalline in nature, uniform and with larger grain size. Current- voltage characteristics under illumination show that the films casted from NiO aged solution are better for perovskite solar cell applications and result in reduced parasitic resistances and enhanced charge transport.

1,2,4-triazole derivatives as potential scaffold for anticonvulsant activity.

The search for new anticonvulsant agent with more selectivity and lower toxicity continues to be an area of rigorous investigation in medicinal chemistry. Epilepsy is a chronic disorder of brain whose treatment consists of controlling seizures with antiepileptic drugs that very often related with side-effects which in rare circumstances can be potentially life-threatening. Triazolam and Alprazolam are established drugs used in epilepsy which have triazole moiety. The potency and broad spectrum of the pharmacological response of triazole moiety as anticonvulsant agent have attracted the attention of medicinal chemists to explore this framework for its potential. The literature shows that different substitution on triazole ring exhibit potent antiepileptic activity with no or lesser neurotoxicity. The present review is a sincere attempt to compile the reported potent triazole derivatives with significant anticonvulsant action.

Realizing green phosphorescent light-emitting materials from rhenium(i) pyrazolato diimine complexes.

Two neutral pyrazolato diimine rhenium(I) carbonyl complexes with formula [Re(CO)(3)(N-N)(btpz)] where N-N = 2,2'-bipyridine (1) and 1,10-phenanathroline (2), and btpz = 3,5-bis(trifluoromethyl) pyrazolate, were synthesized and characterized by elemental analysis, routine spectroscopic methods, and single-crystal X-ray diffraction study. Ground and excited state properties of these complexes were investigated by steady-state and time-resolved spectroscopies. Complexes 1 and 2 show photoluminescent emission in both solution and solid-state at room temperature, arising from metal to ligand charge-transfer (MLCT) transition with strong overlapping of intraligand pi --> pi transitions. The long-lived excited state lifetimes of complexes 1 and 2, which are on the order of microseconds, indicate the presence of phosphorescent emission. As these complexes hold the potential to serve as phosphors for organic light-emitting diodes (OLEDs), their electroluminescent performances were evaluated by employing them as dopants of various electron transport layer (ETL) or hole transport layer (HTL) hosts. For complex 1, a green electrophosphorescence emission centered at lambda(max) = 530 nm was observed at low turn-on voltage ( approximately 6 V) with luminous power efficiency of 0.72 lm/W, external quantum efficiency of 0.82%, and luminance of 2300 cd/m(2) at a current density of 100 mA/cm(2).