Visible-Light-Mediated Amide Synthesis in Deep Eutectic Solvents

In the present study, for the first time environmentally friendly deep eutectic solvents (DESs) are used as reaction media to perform an efficient, simple and straightforward photocatalytic amide synthesis at room temperature using thioacids and amines. This method features mild conditions, a broad substrate scope, high yields (≤99%) under ambient conditions with air and moisture tolerance. Moreover, the applied operationally mild reaction conditions tolerate the presence of several different functional group substituents on the amine counterpart. Finally, the developed approach allows the recycling of the reaction medium and catalyst for at least three consecutive cycles without a significant decrease in the reaction yield.This research has been made possible thanks to the financial support received from the University of Alicante (VIGROB-316FI), the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00) and the Valencian Department of Innovation, Universities, Science and Digital Society (APOSTD/2020/235 and AICO/2021/013). The authors thank the Department of Pharmacy, Health and Nutritional Sciences (Department of Excellence funded according to the Law 232/2016) of the University of Calabria (Italy)

Modafinil induces rapid-onset behavioral sensitization and cross-sensitization with cocaine in mice: implications for the addictive potential of modafinil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on aro7FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)2014/24277-4sem informaçãosem informaçã

An Overview of the Latest Advances in the Catalytic Synthesis of Glycerol Carbonate

In recent years, the development of renewable energy alternatives to traditional fossil fuels has become one of the major challenges all over the world, due to the decline of fossil fuel reserves and their effect on global warming. Biodiesel has become a popular alternative energy source to reduce gas emissions compared to traditional fossil fuels. According to statistics, a nine-fold increase in global biofuel production between 2000 and 2020 was observed. However, its production generates a large amount of glycerol as a by-product, posing an environmental problem when disposed directly in landfills or by incineration. Therefore, low-value glycerol should be converted into high value-added derivatives. As glycerol carbonate is one of the most important derivatives of glycerol, this review aims to discuss the studies over the last ten years about glycerol carbonate synthetic methods, including the typical routes such as phosgene, esterification reaction, urea, oxidative and direct carbonylation as well as several rare synthetic procedures. At the same time, it summarizes the different catalytic reaction systems of each route comparing the advantages and disadvantages of various catalysts and evaluating their catalytic activity. Finally, the future development of glycerol carbonate synthesis is prospected from the point of view of development, technology research and industrialization

An Overview of the Latest Advances in the Catalytic Synthesis of Glycerol Carbonate

In recent years, the development of renewable energy alternatives to traditional fossil fuels has become one of the major challenges all over the world, due to the decline of fossil fuel reserves and their effect on global warming. Biodiesel has become a popular alternative energy source to reduce gas emissions compared to traditional fossil fuels. According to statistics, a nine-fold increase in global biofuel production between 2000 and 2020 was observed. However, its production generates a large amount of glycerol as a by-product, posing an environmental problem when disposed directly in landfills or by incineration. Therefore, low-value glycerol should be converted into high value-added derivatives. As glycerol carbonate is one of the most important derivatives of glycerol, this review aims to discuss the studies over the last ten years about glycerol carbonate synthetic methods, including the typical routes such as phosgene, esterification reaction, urea, oxidative and direct carbonylation as well as several rare synthetic procedures. At the same time, it summarizes the different catalytic reaction systems of each route comparing the advantages and disadvantages of various catalysts and evaluating their catalytic activity. Finally, the future development of glycerol carbonate synthesis is prospected from the point of view of development, technology research and industrialization

Multifunctional Microspheres Based on D-Mannose and Resveratrol for Ciprofloxacin Release

This article describes the preparation, characterization, and performance evaluation of functional microspheres useful for the release of ciprofloxacin. The particles were obtained using D-mannose, a natural aldohexose sugar, and resveratrol, a powerful antioxidant. In particular, the above compounds were initially converted into D-mannose carboxylate and resveratrol methacrylate and, therefore, subjected to an esterification reaction. The resulting product was used for the preparation of the microspheres which were characterized by light scattering, FT-IR spectrophotometry and scanning electron microscopy (SEM). Subsequently, their degree of bloating was evaluated at pH 1.2 to simulate the pH of the stomach, at pH 6.8 and pH 7.4 to mimic the intestinal environment. The antibiotic ciprofloxacin was then loaded into the microspheres, with an encapsulation efficiency of 100%. The cumulative amount of drug released was 55% at pH 6.8 and 99% at pH 7.4. The tests conducted to evaluate the antibacterial activity demonstrated the ability of the microspheres obtained to inhibit the growth of Escherichia coli. The antioxidant efficacy, due to the presence of resveratrol in their structure, was confirmed using rat liver microsomal membranes. The results obtained have highlighted how the microspheres based on D-mannose and resveratrol can be considered promising multifunctional vectors useful in the treatment of intestinal and urinary infections

A Brønsted Acidic Deep Eutectic Solvent for <i>N</i>-Boc Deprotection

The tert-butyloxycarbonyl (Boc) group is one of the most widely used amine-protecting groups in multistep reactions in synthetic organic chemistry as well as in peptide synthesis. Traditional methods to remove the Boc group have disadvantages in terms of high acidity, the use of expensive reagents, excessive amounts of catalysts and harmful solvents as well as high temperatures, making them environmentally unsustainable. Therefore, more efforts must be stepwise tightened to make Boc removal practical, clean, and minimize any potential impact. We describe an efficient and sustainable method for N-Boc deprotection by means of a choline chloride/p-toluenesulfonic acid deep eutectic solvent (DES), which is used as a reaction medium plus catalyst. The adopted conditions allow the deprotection of a wide variety of N-Boc derivatives in excellent yields. The strategy has found advantages in greening, simplicity, and short reaction times, resulting in a useful alternative to standard methods

Sustainable Synthesis of the Active Pharmaceutical Ingredient Atenolol in Deep Eutectic Solvents

Atenolol, one of the top five best-selling drugs in the world today used to treat angina and hypertension, and to reduce the risk of death after a heart attack, faces challenges in current synthetic methods to address inefficiencies and environmental concerns. The traditional synthesis of this drug involves a process that generates a large amount of waste and other by-products that need disposal. This study presents a one-pot DES-based sustainable protocol for synthesizing atenolol. The use of the DES allowed the entire process to be conducted with no need for additional bases or catalysts, in short reaction times, under mild conditions, and avoiding chromatographic purification. The overall yield of atenolol was 95%. The scalability of the process to gram-scale production was successfully demonstrated, emphasizing its potential in industrial applications. Finally, the ‘greenness’ evaluation, performed using the First Pass CHEM21 Metrics Toolkit, highlighted the superiority in terms of the atom economy, the reaction mass efficiency, and the overall process mass intensity of the DES-based synthesis compared with the already existing methods

A Br&oslash;nsted Acidic Deep Eutectic Solvent for N-Boc Deprotection

The tert-butyloxycarbonyl (Boc) group is one of the most widely used amine-protecting groups in multistep reactions in synthetic organic chemistry as well as in peptide synthesis. Traditional methods to remove the Boc group have disadvantages in terms of high acidity, the use of expensive reagents, excessive amounts of catalysts and harmful solvents as well as high temperatures, making them environmentally unsustainable. Therefore, more efforts must be stepwise tightened to make Boc removal practical, clean, and minimize any potential impact. We describe an efficient and sustainable method for N-Boc deprotection by means of a choline chloride/p-toluenesulfonic acid deep eutectic solvent (DES), which is used as a reaction medium plus catalyst. The adopted conditions allow the deprotection of a wide variety of N-Boc derivatives in excellent yields. The strategy has found advantages in greening, simplicity, and short reaction times, resulting in a useful alternative to standard methods

Deep Eutectic Solvents for Improving the Solubilization and Delivery of Dapsone

Owing to a growing awareness toward environmental impact, the use of safer and eco-friendly solvents like deep eutectic solvents (DESs), has recently undergone important growth in the pharmaceutical field, with regard to their application as non-aqueous liquid administration vehicles, since they do not carry the same risks of toxicity and handling as traditional organic solvents. Major attention has been given to the development of advantageous transdermal drug delivery systems, because of their ease of use and better acceptability. Here, we report the use of two different DESs, based on choline chloride, used as hydrogen bond acceptor (HBA), and ascorbic acid or propylene glycol, used as hydrogen bond donors (HBDs), able to enhance the solubility and the topical delivery of dapsone, representing a class IV drug. The interactions between the DESs’ components and the drug were studied by performing DSC, FT-IR, and NMR analysis of the eutectic systems and the pure drug, confirming the establishment of H-bonds between the drug and the DESs’ components. Diffusion and permeability studies, carried out in a Franz cell, showed an increase in permeability, highlighting the great potential of DESs as dissolution and permeation enhancers in the development of novel and more effective drug delivery systems in topical administration

Reactive Deep Eutectic Solvent for an Eco-Friendly Synthesis of Cellulose Carbamate

The limited solubility of natural cellulose in water and common organic solvents hinders its diverse applications, despite being one of the most abundant and easily accessible biopolymers on Earth. Chemical derivatization, such as cellulose carbamate (CC), offers a pathway to enhance both solubility and industrial processability. In this study, CC was synthesized by exploiting a novel type IV deep eutectic solvent (DES) composed of erbium trichloride and urea. This DES was shown to be not only an environmentally friendly reaction medium/catalyst but also actively participated in the synthetic process as a reagent. The resultant cellulose carbamate samples were characterized through FT-IR and elemental analysis. A nitrogen content value of 1.59% was afforded determining a degree of substitution corresponding to a value of 0.19. One of the key scientific advancements lies in the preparation of cellulose carbamate using a straightforward and cost-effective method. This approach utilizes non-toxic compounds, aligning with the principles of green chemistry and contributing to sustainable development in cellulose derivative production