Benzazole-Based ESIPT Fluorophores: Proton Transfer from the Chalcogen Perspective. A Combined Theoretical and Experimental Study.

In this study, we present a comprehensive photophysical investigation of ESIPT-reactive benzazole derivatives in both solution and the solid state. These derivatives incorporate different chalcogen atoms (O, S, and Se) into their structures, and we explore how these variations impact their electronic properties in both ground and excited states. Changes in the UV-Vis absorption and fluorescence emission spectra were analyzed and correlated with the chalcogen atom and solvent polarity. In general, the spectral band of the benzazole derivative containing selenium was redshifted in both the ground and excited states compared to that of its oxygen and sulfur counterparts. Furthermore, we observed that the solvent played a distinctive role in influencing the ESIPT process within these compounds, underscoring once again the significant influence of the chalcogen atom on their photophysical behavior. Theoretical calculations provided a deeper understanding of the molecular dynamics, electronic structures, and photophysical properties of these compounds. These calculations highlighted the effect of chalcogen atoms on the molecular geometry, absorption and emission characteristics, and intramolecular hydrogen bonding, revealing intricate details of the ESIPT mechanism. The integration of experimental and computational data offers a detailed view of the structural and electronic factors governing the photophysical behavior of benzazole derivatives.

Synthesis of Isoxazolines by the Electrophilic Chalcogenation of ß,γ-Unsaturated Oximes: Fishing Novel Anti-Inflammatory Agents.

Herein, we describe a new strategy to prepare chalcogen-functionalized isoxazolines. The strategy involves the reaction of ß,γ-unsaturated oximes with electrophilic selenium and tellurium species, affording 19 new selenium- and tellurium-containing isoxazolines in good yields after 1 h at room temperature. The method was efficiently extended to the synthesis of 5 new (bis)isoxazoline ditellurides. One of the prepared compounds, 3-phenyl-5-((phenylselanyl)methyl)-isoxazoline, demonstrated better anti-inflammatory and antiedematogenic effects than the reference drug Celecoxib.

Synthesis of Terminal Ethynyl Aryl Selenides and Sulfides Based on the Retro-Favorskii Reaction of Hydroxypropargyl Precursors.

The retro-Favorskii reaction is an excellent way to achieve terminal alkynes. Methodologies that connect the synthesis of terminal alkynes and organochalcogen motifs are important for the construction of novel compounds. Fourteen new terminal alkynes containing either Csp -S or Csp -Se bonds were selectively prepared through the retro-Favorskii reaction from the respective carbinol precursors. It was discovered that terminal chalcogen alkynes were stable for weeks if stored as a solution in hexanes.

Photoinduced metal-free α-selenylation of ketones.

Herein, we report an efficient photoinduced α-selenylation of ketones without metal, additives or under photosensitizer-free conditions, providing a green protocol using light energy to synthesize a variety of α-selenoketones. This new methodology proved to be a mild, simple and eco-friendly tool for the efficient synthesis of the desired products.

Ultrasound-promoted regioselective synthesis of chalcogeno-indolizines by a stepwise 1,3-dipolar cycloaddition.

A series of new organochalcogen derivatives of indolizines was synthesized in moderate to excellent yields from pyridinium salts and chalcogeno-alkynes. The reaction can be carried out under thermal conditions or by sonochemical processes in short reaction times. The stepwise cycloaddition reaction forming chalcogeno-indolizines is regioselective and extends to a broad range of functional groups. Furthermore, novel chalcogeno-alkynes are reported and the first derivatives of teluro-indolizine are described. The influence of selenium functionalization on the photophysical properties of indolizines is also described, in which the compounds showed absorption in the UV-Vis region around 360 nm and emission in the blue-to-green region. Relatively low fluorescence quantum yield (ϕfl) values were calculated, in agreement with the chalcogen effect on other heterocycles.

Rational design, cognition and neuropathology evaluation of QTC-4-MeOBnE in a streptozotocin-induced mouse model of sporadic Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial pathology characterized by amyloid deposits, neurofibrillary formation, oxidative stress and cholinergic system dysfunction. In this sense, here we report the rational design of a multi-target directed ligand (MTDL) for AD based on virtual screening and bioinformatic analyses, exploring the molecular targets ß-secretase (BACE-1), glycogen synthase kinase-3ß (GSK-3ß) and acetylcholinesterase (AChE). After this screening, the compound with higher molecular docking affinity was selected, the 1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4 carboxamide(QTC-4-MeOBnE). To further our studies, the protective effect of QTC-4-MeOBnE (0.1 and 1 mg/kg for 20 days) on STZ-induced sporadic AD mice was determined. QTC-4-MeOBnE pretreatment attenuated cognitive and memory deficit induced by STZ in an object recognition test, Y-maze, social recognition test and step-down passive avoidance. The mechanisms underlying this action might be attributed to the reduction of lipid peroxidation and reactive species formation in the prefrontal cortex and hippocampus of mice submitted to STZ. In addition, QTC-4-MeOBnE pretreatment abolished the up-regulation of AChE activity and the overexpression of GSK 3ß and genes involved in amyloid cascade such as BACE-1, protein precursor amyloid, у-secretase, induced by STZ. Moreover, toxicological parameters were not modified by QTC-4-MeOBnE chronic treatment. This evidence suggests that QTC-4-MeOBnE exerts its therapeutic effect through multiple pathways involved in AD.