Project description:Column chromatography is a technique widely used for the purification of active pharmaceutical ingredients (APIs). One of the common solvent systems used by this technique is blends of dichloromethane (DCM) and methanol (MeOH), thereby exposing workers to health and safety risks and making the pharmaceutical sector one of the major contributors to chlorinated solvent waste. In this work, API separation and purification using several alternative safer solvent blends in column chromatography were evaluated and compared to DCM/MeOH. Ibuprofen and acetaminophen were used as model APIs, and caffeine was used as a model additive. Overall, some of the safer solvent blends tested provided better performance, with higher API recovery and purity compared to DCM/MeOH, in addition to potential health, safety, and environmental benefits. Specifically, blends of heptane/ethyl acetate and heptane/methyl acetate showed the most promise. Our work demonstrates the potential of these safer solvent blends as possible replacements for DCM/MeOH in API purification, thereby addressing a critical safety concern in the pharmaceutical industry.
Project description:Glycolipids are considered an alternative to petrochemically based surfactants because they are non-toxic, biodegradable, and less harmful to the environment while having comparable surface-active properties. They can be produced chemically or enzymatically in organic solvents or in deep eutectic solvents (DES) from renewable resources. DES are non-flammable, non-volatile, biodegradable, and almost non-toxic. Unlike organic solvents, sugars are easily soluble in hydrophilic DES. However, DES are highly viscous systems and restricted mass transfer is likely to be a major limiting factor for their application. Limiting factors for glycolipid synthesis in DES are not generally well understood. Therefore, the influence of external mass transfer, fatty acid concentration, and distribution on initial reaction velocity in two hydrophilic DES (choline:urea and choline:glucose) was investigated. At agitation speeds of and higher than 60 rpm, the viscosity of both DES did not limit external mass transfer. Fatty acid concentration of 0.5 M resulted in highest initial reaction velocity while higher concentrations had negative effects. Fatty acid accessibility was identified as a limiting factor for glycolipid synthesis in hydrophilic DES. Mean droplet sizes of fatty acid-DES emulsions can be significantly decreased by ultrasonic pretreatment resulting in significantly increased initial reaction velocity and yield (from 0.15 ± 0.03 μmol glucose monodecanoate/g DES to 0.57 ± 0.03 μmol/g) in the choline: urea DES. The study clearly indicates that fatty acid accessibility is a limiting factor in enzymatic glycolipid synthesis in DES. Furthermore, it was shown that physical pretreatment of fatty acid-DES emulsions is mandatory to improve the availability of fatty acids.
Project description:The traditional use of organic solvents in various branches of industry is being rethought as these compounds very often display high volatility, toxicity and lipophilicity (related to the ability to interact with biological membranes). More recently, developments in the field of Green Chemistry are focusing on the design of more sustainable and cost-effective solvent alternatives like Ionic Liquids (ILs), bio-based solvents and natural deep eutectic solvents (NADESs). The present study aimed at performing an ecotoxicological screening of 15 NADESs using an extensive set of marine and freshwater bioassays, based on different endpoints as the following: immobilization of the crustacean Daphnia magna, growth inhibition of Raphidocelis subcapitata and of Phaeodactylum tricornutum, larval development alterations on the serpulid Ficopomatus enigmaticus and bioluminescence inhibition of Aliivibrio fischeri. What emerged was a general absence of toxicity of all samples. However, both algal assays showed a certain degree of biostimulation, up to over 100% growth increase in respect to controls with 8 out of 15 compounds tested with Raphidocelis subcapitata. Despite NADESs-induced negligible toxicity effects to invertebrates, encouraging their labelling as "sustainable" solvents, the liability of their intentional or accidental release into aquatic systems may represent a serious risk in terms of ecosystem functioning impairments.
Project description:A deep eutectic solvent (DES) is a mixture of two or more chemicals that interact via hydrogen bonding and has a melting point far below that of the individual components. DESs have been proposed as alternative solvents for poorly soluble active pharmaceutical ingredients (API). In this study, the solvation capacities of six deep eutectic solvents were compared to water and three conventional pharmaceutical solvents (PEG 300, ethanol and glycerol) for 11 APIs. The experimentally determined solubilities were compared to computational solubilities predicted by the Conductor-like Screening Model for Real Solvents (COSMO-RS). While the conventional pharmaceutical solvents PEG 300 and ethanol were the best solvents for the majority of the studied APIs, API-DES combinations were identified, which exceeded the API solubility found in the conventional pharmaceutical solvents. Furthermore, it was also possible to obtain high solubilities in the DESs relative to water, suggesting DESs to be potential solvents for poorly water soluble APIs. In addition, the relative increase in solubility found in the experimental data could be well predicted ab initio using COSMO-RS. Hence, COSMO-RS may in the future be used to reduce the experimental screening of potential DESs for a given API.
Project description:The high tunability of deep eutectic solvents (DESs) stems from the ease of changing their precursors and relative compositions. However, measuring the physicochemical properties across large composition and temperature ranges, necessary to properly design target-specific DESs, is tedious and error-prone and represents a bottleneck in the advancement and scalability of DES-based applications. As such, active learning (AL) methodologies based on Gaussian processes (GPs) were developed in this work to minimize the experimental effort necessary to characterize DESs. Owing to its importance for large-scale applications, the reduction of DES viscosity through the addition of a low-molecular-weight solvent was explored as a case study. A high-throughput experimental screening was initially performed on nine different ternary DESs. Then, GPs were successfully trained to predict DES viscosity from its composition and temperature, showcasing the ability of these stochastic, nonparametric models to accurately describe the physicochemical properties of complex mixtures. Finally, the ability of GPs to provide estimates of their own uncertainty was leveraged through an AL framework to minimize the number of data points necessary to obtain accurate viscosity modes. This led to a significant reduction in data requirements, with many systems requiring only five independent viscosity data points to be properly described.
Project description:The continuous flow, enantioselective, organophotoredox catalytic asymmetric alkylation of aldehydes was studied, by using a homemade, custom-designed photoreactor for reactions under cryogenic conditions. Going from microfluidic conditions up to a 10 mL mesofluidic reactor, an increase of productivity by almost 18000 % compared to the batch reaction was demonstrated. Finally, for the first time, a stereoselective photoredox organocatalytic continuous flow reaction in a fully telescoped process for an active pharmaceutical ingredient (API)synthesis was successfully achieved. The final process consists of four units of operation: visible light-driven asymmetric catalytic benzylation under continuous flow, inline continuous work-up, neutralisation and a final oxidative amidation step afforded the pharmaceutically active molecule in 95 % e.e.
Project description:Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery.
Project description:Deep eutectic solvents (DESs) are eutectic mixtures of salts and hydrogen bond donors with melting points low enough to be used as solvents. DESs have proved to be a good alternative to traditional organic solvents and ionic liquids (ILs) in many biocatalytic processes. Apart from the benign characteristics similar to those of ILs (e.g., low volatility, low inflammability and low melting point), DESs have their unique merits of easy preparation and low cost owing to their renewable and available raw materials. To better apply such solvents in green and sustainable chemistry, this review firstly describes some basic properties, mainly the toxicity and biodegradability of DESs. Secondly, it presents several valuable applications of DES as solvent/co-solvent in biocatalytic reactions, such as lipase-catalyzed transesterification and ester hydrolysis reactions. The roles, serving as extractive reagent for an enzymatic product and pretreatment solvent of enzymatic biomass hydrolysis, are also discussed. Further understanding how DESs affect biocatalytic reaction will facilitate the design of novel solvents and contribute to the discovery of new reactions in these solvents.
Project description:The citrus industry produces large amounts of waste rich in bioactive compounds that have important effects on human health. Their extraction was performed using organic solvents, and a greener alternative to those solvents are natural deep eutectic solvents (NADES). The present study aimed to obtain and optimize extracts rich in polyphenols and flavonoids from orange peels using NADES and monitor polyphenol stability in the extracts for 30 days. The software COSMOtherm (conductor-like screening model) was used to screen fourteen NADES. The most promising solvents were lactic acid:glucose (LA:Glu) with an extraction yield of 1932 ± 7.83 mgGAE/100 gdw for TPC (total polyphenol content) and 82.7 ± 3.0 mg/100 gdw for TFC (total flavonoid content) and in the case of L-proline:malic acid (LP:MA) was 2164 ± 5.17 mgGAE/100 gdw for TPC and 97.0 ± 1.65 mg/100 gdw for TFC. The extraction process using LA:Glu and LP:MA was optimized, and the results showed that the selected variables (%NADES, solid:liquid ratio, and extraction time) had a significant influence on the extraction of TPC and TFC. Results showed that NADES improve the stability of TPC. These findings revealed that NADES are efficient for the extraction of bioactive compounds from orange by-products, and these extracts can represent an alternative for the food industry to enrich food products with natural ingredients.
Project description:A high-yield one-pot two-step synthesis of 2-aminoimidazoles (2-AI), exploiting an under-air heterocyclodehydration process between α-chloroketones and guanidine derivatives, and using deep eutectic solvents (DESs) as nonconventional, "green" and "innocent" reaction media, has been accomplished successfully. The combination of either glycerol or urea with choline chloride (ChCl) proved to be effective for decreasing the reaction time to about 4-6 h in contrast to the 10-12 h usually required for the same reaction run in toxic and volatile organic solvents and under an argon atmosphere. In addition, the use of the ChCl-urea as a DES also enables the direct isolation of triaryl-substituted 2-AI derivatives by means of a simple work-up procedure consisting in filtration and crystallization, and allows the recycle of the DES mixture. A plausible mechanism highlighting the potential role played by hydrogen bonding catalysis has also been illustrated.