Glycerol as Reaction Medium for Sonogashira Couplings: A Green Approach for the Synthesis of New Triarylamine-Based Materials with Potential Application in Optoelectronics.

This study focuses on the design, eco-friendly synthesis, and characterization of several novel three-legged triphenylamine derivatives. By performing Sonogashira couplings of functionalized aryl iodides with tris(4-ethynylphenyl)amine in glycerol, a readily available bio-derived solvent, we achieved the synthesis of target products in short times and high yields, up to 94%, with consistently lower E-factors and reduced costs compared to standard conditions using toluene as the reaction medium. The target molecules possess a D-(π-A)3 or D-(π-D)3 structure, where an electron-donating core connects to three electron-donating (D) or electron-accepting (A) peripheral aromatic subunits through an acetylene spacer. Their main optical and electronic properties have been determined experimentally and by DFT simulations and suggest a possible implementation in energy conversion technologies such as luminescent solar concentrators (LSCs) and perovskite solar cells (PSCs).

N-Butylpyrrolidinone is an equally good solvent as N,N-dimethylformamide for microwave assisted solid phase peptide synthesis.

Solid-phase peptide synthesis (SPPS) is the prevailing method for synthesizing research peptides today. However, SPPS is associated with a significant environmental concern due to the utilization of hazardous solvents such as N,N-dimethylformamide (DMF) or N-methylpyrrolidone, which generate substantial waste. In light of this, our research endeavors to identify more environmentally friendly solvents for SPPS. In this study, we have assessed the suitability of five green solvents as alternatives to DMF in microwave assisted SPPS. The solvents evaluated include Cyrene, ethyl acetate, 1,3-dioxolane, tetrahydro-2-methylfuran, and N-Butylpyrrolidinone (NBP). Our investigation encompassed all stages of the synthesis process, from resin swelling, dissolution of reagents, culminating in the successful synthesis of five diverse peptides, including the challenging ACP 65-74, Peptide 18A, Thymosin α1, and Jung-Redemann peptide. Our findings indicate that NBP emerged as a strong contender, performing on par with DMF in all tested syntheses. Furthermore, we observed that combinations of NBP with either ethyl acetate or tetrahydro-2-methylfuran demonstrated excellent results. This research contributes to the pursuit of more sustainable and environmentally conscious practices in peptide synthesis.

Optimization of peptide synthesis time and sustainability using novel eco-friendly binary solvent systems with induction heating on an automated peptide synthesizer.

On December 12th, 2023, the European Commission took regulatory action to amend Annex XVII of REACH, imposing restrictions on the use of N,N-dimethylformamide (DMF) within the EU market owing to its high toxicity. Historically, DMF has been widely considered the gold standard for solid-phase peptide synthesis (SPPS). Being urgent to propose alternative solvents, we tested the suitability of non-hazardous neat and mixed solvents. Notably, binary solvent mixtures containing dimethyl sulfoxide as one of the solvent partners demonstrated high efficacy in solubilizing reagents while maintaining the desired swelling characteristics of common resins. A series of binary solvent mixtures were tested in automated SPPS, both at room temperature and high temperature, employing the PurePep® Chorus synthesizer, which enabled controlled induction heating between 25 and 90°C with oscillation mixing. The performances were assessed in challenging peptide sequences, i.e., ACP (65-74), and in longer and aggregating sequences like SARS-CoV-2 RBM (436-507) and ß-amyloid (1-42). Furthermore, as part of the proposed sustainable approach to minimize the utilization of hazardous solvents, we coupled the novel PurePep EasyClean catch-and-release purification technology. This work, addressing regulatory compliance, emphasizes the crucial role of green chemistry in advancing safer and more environmentally friendly practices in SPPS.

Water as a green solvent for sustainable sample preparation: single drop microextraction of N-nitrosamines from losartan tablets.

Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400 ng g-1, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.

Magnetically Recyclable Nanoscale Zero-Valent Iron-Mediated PhotoRDRP in Ionic Liquid toward Smart, Functional Polymers.

A facile method based on recyclable nanoscale zero-valent iron (nZVI)-mediated photoinduced reversible deactivation radical polymerization in ionic liquid (IL) leads to the synthesis of narrow disperse poly(tert-butyl methacrylate) (PTBMA), amphiphilic PTBMA-block-poly(poly(ethylene glycol)methacrylate) diblock copolymer and double hydrophilic poly(methacrylic acid)-block-poly(poly(ethylene glycol)methacrylate) (PMAA-b-PPEGMA) diblock copolymers thereof. Stimuli response of the synthesized PMAA-b-PPEGMA diblock copolymer against variation in pH and temperature is assessed. Recyclability of the nZVI (catalyst) and IL (solvent) is established. Polymerization may be switched ON or OFF, simply by turning the UVA light irradiation ON or OFF, offering temporal control. The diblock copolymer self-aggregates into spherical nanoaggregates which are employed for encapsulation of coumarin 102 (C102, a typical hydrophobic dye), describing their potential application in drug delivery applications. The facile synthesis strategy may open up new avenues for the preparation of intelligent functional polymers for engineering and biomedical applications.

Eco-friendly micellar HPLC approach for simultaneous estimation of combination therapy for hidradenitis suppurativa: Applications to spiked human plasma and different dosage forms.

This study introduces a new method for analyzing rifampicin, moxifloxacin, and metronidazole using a green micellar High Performance Liquid Chromatography-Ultraviolet method in bulk drugs, different commercial formulations, and spiked human plasma. The combined therapy of these three broad-spectrum antibiotics is used to cure refractory hidradenitis suppurativa (HS), an inflammatory condition affecting the skin. The sustainable separation was attained on a reversed-phase C18 Kinetex® column maintained at ambient temperature in less than 5 min. The mobile phase comprises 0.1 M sodium dodecyl sulfate (SDS) in water, pH 3.5, adjusted using o-phosphoric acid, and 10% n-butanol. The flow rate was 1 mL/min, with 10 µL injection volume and UV detection at 230 nm. The impact of three key significant variables, SDS concentration, n-butanol percentage, and the mobile phase pH, on suitability parameters was studied. ICH and FDA guidelines were committed to when validating the technique. The results showed linear calibration graphs with high precision and accuracy, in both pure and spiked plasma. The method is efficient, easy to use, and has a high sample throughput, making it suitable for routine analysis in the quality control department and therapeutic monitoring. It is also evaluated as a green-and-white substitute for traditional reported methods.

Developing a recovery process for bioactives from discarded by-products of winemaking industry based on multivariate optimization method: Deep eutectic solvents as eco-friendly extraction media.

INTRODUCTION: The recovery process for bioactives from discarded by-products of the winemaking industry is of great value considering both environmental and economic aspects. OBJECTIVE: The goal of this study is to investigate the extraction of phenolic antioxidants from grape (Vitis vinifera) seeds by means of carboxylic acid-based deep eutectic solvents (DESs) in order to propose an environmentally friendly method based on a multivariate optimization approach. MATERIAL AND METHODS: Carboxylic acid-based DESs were designed with several molar ratios (1/1, 1/2, and 2/1). Two polyols (glycerol and ethylene glycol) were used as hydrogen bond donors, while formic acid, acetic acid, and propionic acid were selected as hydrogen bond acceptors. The process parameters (water content, extraction time, and solid mass) were analyzed to optimize the process through Box-Behnken design with response surface method, after determination of the best combination for the highest total phenolic content (TPC) and the antioxidant activity yields. RESULTS: The maximum TPC yield (153.17 ± 0.003 mg-GAE/g-GS) and antioxidant activity yield (82.26 ± 0.004 mg-GAE/g-GS) were achieved by 50% water addition into the DES (ethylene glycol/acetic acid, 1/1), 85 sec extraction time, and 0.1 g grape seed.

The Application of Green Solvents in the Synthesis of S-Heterocyclic Compounds-A Review.

Cyclic organic compounds containing sulfur atoms constitute a large group, and they play an important role in the chemistry of heterocyclic compounds. They are valuable intermediates for the synthesis of other compounds or biologically active compounds themselves. The synthesis of heterocyclic compounds poses a major challenge for organic chemists, especially in the context of applying the principles of "green chemistry". This work is a review of the methods of synthesis of various S-heterocyclic compounds using green solvents such as water, ionic liquids, deep eutectic solvents, glycerol, ethylene glycol, polyethylene glycol, and sabinene. The syntheses of five-, six-, and seven-membered heterocyclic compounds containing a sulfur atom or atoms, as well as those with other heteroatoms and fused-ring systems, are described. It is shown that using green solvents determines the attractiveness of conditions for many reactions; for others, such use constitutes a real compromise between efficiency and mild reaction conditions.

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.

Eco-friendly solvent-based liquid-liquid extraction of phenolic acids from winery wastewater streams.

This study proposes liquid-liquid extraction (LLE) for the recovery of phenolic acids from winery wastewater replacing common volatile organic compounds (VOCs) with environmentally friendly solvents. On one hand, terpenes (α-pinene and p-cymene) and terpenoids (eucalyptol and linalool) were selected as green solvents and compared to common VOCs (ethyl acetate or 1-butanol). On the other hand, gallic acid (GA), vanillic acid (VA), syringic acid (SA) and caffeic acid (CA) were selected as phenolic acids to be recovered. The extraction performance was evaluated under different operation conditions: solvent-to-feed ratio, initial concentration of phenolic acids and temperature. This work also evaluated the back-extraction whole process global recovery and solvent regeneration, by means of aqueous NaOH solution. Eucalyptol has shown the highest overall global extraction performance (21.07 % for GA, 93.21 % for VA, 78.79 % for SA, and 80.57 % for CA) and lower water solubility compared to the best performing VOC solvent (1-butanol). Therefore, eucalyptol can be a potential eco-friendly solvent to replace VOCs for sustainable phenolic acid recovery from winery wastewater. Finally, to ensure a clean water stream after the LLE, the traces of solvent were completely removed by electrooxidation with boron-doped diamond anode at a current density of 422.54 A/m2.

Recovery and separation of glycyrrhizic acid from Natural Deep Eutectic Solvent (NADES) extract by macroporous resin: adsorption kinetics and isotherm studies.

Natural Deep Eutectic Solvents (NADESs) have emerged as a green and sustainable alternative to conventional organic solvents to extract bioactive compounds. However, the recovery of bioactive compounds from the NADES extracts is challenging, restricting their large-scale applications. The present work investigated the recovery of glycyrrhizic acid (GA) from choline-chloride/lactic acid NADES extract using macroporous resins. GA possesses a wide spectrum of biological activities, and it is extracted from the well-known herb Glycyrrhiza glabra. During resin screening, DIAIONTM SP700 showed high adsorption and desorption capacities. The adsorption kinetics study demonstrated that the adsorption of GA on SP700 followed Pseudo First-order kinetic model. Moreover, the adsorption behaviors were elucidated by the Freundlich isotherm using a correlation coefficient based on a static adsorption study at different temperatures and pH. Furthermore, the thermodynamic parameters, for instance, the change of Gibbs free energy (ΔG*), entropy (ΔS*), and enthalpy (ΔH*), showed that the adsorption process was spontaneous, favorable and exothermic. In addition, the sample after macroporous resin treatment, which is enriched with GA exhibited good anticancer potential analyzed by SRB assay. The regenerated NADES solvent was recycled twice, keeping more than 90% extraction efficiency, indicating good reusability of NADES in the GA extraction process by using macroporous resin.

Aromas: Lovely to Smell and Nice Solvents for Polyphenols? Curcumin Solubilisation Power of Fragrances and Flavours.

Natural aromas like cinnamaldehyde are suitable solvents to extract curcuminoids, the active ingredients found in the rhizomes of Curcuma longa L. In a pursuit to find other nature-based solvents, capable of solving curcumin, forty fragrances and flavours were investigated in terms of their solubilisation power. Aroma compounds were selected according to their molecular structure and functional groups. Their capabilities of solving curcumin were examined by UV-Vis spectroscopy and COSMO-RS calculations. The trends of these calculations were in accordance with the experimental solubilisation trend of the solubility screening and a list with the respective curcumin concentrations is given; σ-profiles and Gibbs free energy were considered to further investigate the solubilisation process of curcumin, which was found to be based on hydrogen bonding. High curcumin solubility was achieved in the presence of solvent (mixtures) with high hydrogen-bond-acceptor and low hydrogen-bond-donor abilities, like γ- and δ-lactones. The special case of DMSO was also examined, as the highest curcumin solubility was observed with it. Possible specific interactions of selected aroma compounds (citral and δ-hexalactone) with curcumin were investigated via 1H NMR and NOESY experiments. The tested flavours and fragrances were evaluated regarding their potential as green alternative solvents.

Advancements in Aqueous Two-Phase Systems for Enzyme Extraction, Purification, and Biotransformation.

In recent years, the increasing need for energy conservation and environmental protection has driven industries to explore more efficient and sustainable processes. Liquid-liquid extraction (LLE) is a common method used in various sectors for separating components of liquid mixtures. However, the traditional use of toxic solvents poses significant health and environmental risks, prompting the shift toward green solvents. This review deals with the principles, applications, and advantages of aqueous two-phase systems (ATPS) as an alternative to conventional LLE. ATPS, which typically utilize water and nontoxic components, offer significant benefits such as high purity and single-step biomolecule extraction. This paper explores the thermodynamic principles of ATPS, factors influencing enzyme partitioning, and recent advancements in the field. Specific emphasis is placed on the use of ATPS for enzyme extraction, showcasing its potential in improving yields and purity while minimizing environmental impact. The review also highlights the role of ionic liquids and deep eutectic solvents in enhancing the efficiency of ATPS, making them viable for industrial applications. The discussion extends to the challenges of integrating ATPS into biotransformation processes, including enzyme stability and process optimization. Through comprehensive analysis, this paper aims to provide insights into the future prospects of ATPS in sustainable industrial practices and biotechnological applications.

Tuning Ferulic Acid Solubility in Choline-Chloride- and Betaine-Based Deep Eutectic Solvents: Experimental Determination and Machine Learning Modeling.

Deep eutectic solvents (DES) represent a promising class of green solvents, offering particular utility in the extraction and development of new formulations of natural compounds such as ferulic acid (FA). The experimental phase of the study undertook a systematic investigation of the solubility of FA in DES, comprising choline chloride or betaine as hydrogen bond acceptors and six different polyols as hydrogen bond donors. The results demonstrated that solvents based on choline chloride were more effective than those based on betaine. The optimal ratio of hydrogen bond acceptors to donors was found to be 1:2 molar. The addition of water to the DES resulted in a notable enhancement in the solubility of FA. Among the polyols tested, triethylene glycol was the most effective. Hence, DES composed of choline chloride and triethylene glycol (TEG) (1:2) with added water in a 0.3 molar ration is suggested as an efficient alternative to traditional organic solvents like DMSO. In the second part of this report, the affinities of FA in saturated solutions were computed for solute-solute and all solute-solvent pairs. It was found that self-association of FA leads to a cyclic structure of the C28 type, common among carboxylic acids, which is the strongest type of FA affinity. On the other hand, among all hetero-molecular bi-complexes, the most stable is the FA-TEG pair, which is an interesting congruency with the high solubility of FA in TEG containing liquids. Finally, this work combined COSMO-RS modeling with machine learning for the development of a model predicting ferulic acid solubility in a wide range of solvents, including not only DES but also classical neat and binary mixtures. A machine learning protocol developed a highly accurate model for predicting FA solubility, significantly outperforming the COSMO-RS approach. Based on the obtained results, it is recommended to use the support vector regressor (SVR) for screening new dissolution media as it is not only accurate but also has sound generalization to new systems.

Experimental and Theoretical Insights into the Intermolecular Interactions in Saturated Systems of Dapsone in Conventional and Deep Eutectic Solvents.

Solubility is not only a crucial physicochemical property for laboratory practice but also provides valuable insight into the mechanism of saturated system organization, as a measure of the interplay between various intermolecular interactions. The importance of these data cannot be overstated, particularly when dealing with active pharmaceutical ingredients (APIs), such as dapsone. It is a commonly used anti-inflammatory and antimicrobial agent. However, its low solubility hampers its efficient applications. In this project, deep eutectic solvents (DESs) were used as solubilizing agents for dapsone as an alternative to traditional solvents. DESs were composed of choline chloride and one of six polyols. Additionally, water-DES mixtures were studied as a type of ternary solvents. The solubility of dapsone in these systems was determined spectrophotometrically. This study also analyzed the intermolecular interactions, not only in the studied eutectic systems, but also in a wide range of systems found in the literature, determined using the COSMO-RS framework. The intermolecular interactions were quantified as affinity values, which correspond to the Gibbs free energy of pair formation of dapsone molecules with constituents of regular solvents and choline chloride-based deep eutectic solvents. The patterns of solute-solute, solute-solvent, and solvent-solvent interactions that affect solubility were recognized using Orange data mining software (version 3.36.2). Finally, the computed affinity values were used to provide useful descriptors for machine learning purposes. The impact of intermolecular interactions on dapsone solubility in neat solvents, binary organic solvent mixtures, and deep eutectic solvents was analyzed and highlighted, underscoring the crucial role of dapsone self-association and providing valuable insights into complex solubility phenomena. Also the importance of solvent-solvent diversity was highlighted as a factor determining dapsone solubility. The Non-Linear Support Vector Regression (NuSVR) model, in conjunction with unique molecular descriptors, revealed exceptional predictive accuracy. Overall, this study underscores the potency of computed molecular characteristics and machine learning models in unraveling complex molecular interactions, thereby advancing our understanding of solubility phenomena within the scientific community.

Spark Discharge Doping-Achieving Unprecedented Control over Aggregate Fraction and Backbone Ordering in Poly(3-hexylthiophene) Solutions.

The properties of semiconducting polymers are strongly influenced by their aggregation behavior, that is, their aggregate fraction and backbone planarity. However, tuning these properties, particularly the backbone planarity, is challenging. This work introduces a novel solution treatment to precisely control the aggregation of semiconducting polymers, namely current-induced doping (CID). It utilizes spark discharges between two electrodes immersed in a polymer solution to create strong electrical currents resulting in temporary doping of the polymer. Rapid doping-induced aggregation occurs upon every treatment step for the semiconducting model-polymer poly(3-hexylthiophene). Therefore, the aggregate fraction in solution can be precisely tuned up to a maximum value determined by the solubility of the doped state. A qualitative model for the dependences of the achievable aggregate fraction on the CID treatment strength and various solution parameters is presented. Moreover, the CID treatment can yield an extraordinarily high quality of backbone order and planarization, expressed in UV-vis absorption spectroscopy and differential scanning calorimetry measurements. Depending on the selected parameters, an arbitrarily lower backbone order can be chosen using the CID treatment, allowing for maximum control of aggregation. This method may become an elegant pathway to finely tune aggregation and solid-state morphology for thin-films of semiconducting polymers.

New Generation of Benzidine Wide-Gap Conjugated Materials: Solution Processing a Classic Evaporated Scaffold.

Carbazole- and fluorene-substituted benzidine blocks have been functionalized with two different solubilizing pendant groups, in order to enhance the material's solubility in greener solvents. Preserving the optical and electrochemical properties, the aromatic function and substitution showed an important influence on the solvent affinity, achieving concentrations up to 150 mg/mL in o-xylenes for the glycol-containing materials and decent solubility in alcohols for the compounds functionalized with ionic chains. The latter solution proved to be ideal for the preparation of luminescence slot-die coating film on top of flexible-substrates up to 33 cm×2 cm. As a proof of concept, the materials have been implemented in different organic electronic devices, highlighting the low turn-on voltage (4 V) presented by organic light-emitting diodes (OLEDs), which is comparable with vacuum-processed devices. A structure-solubility relationship and a synthetic strategy are disentangled in this manuscript to tailor organic semiconductors and adapt their solubility towards the desired solvent and application.

Insights into using green and unconventional technologies to recover natural astaxanthin from microbial biomass.

Microorganisms such as bacteria, microalgae and fungi, are natural and rich sources of several valuable bioactive antioxidant's compounds, including carotenoids. Among the carotenoids with antioxidant properties, astaxanthin can be highlighted due to its pharmaceutical, feed, food, cosmetic and biotechnological applications. The best-known producers of astaxanthin are yeast and microalgae cells that biosynthesize this pigment intracellularly, requiring efficient and sustainable downstream procedures for its recovery. Conventional multi-step procedures usually involve the consumption of large amounts of volatile organic compounds (VOCs), which are regarded as toxic and hazardous chemicals. Considering these environmental issues, this review is focused on revealing the potential of unconventional extraction procedures [viz., Supercritical Fluid Extraction (SFE), Ultrasound-Assisted Extraction (UAE), Microwave-Assisted Extraction (MAE), High-Pressure Homogenization (HPH)] combined with alternative green solvents (biosolvents, eutectic solvents and ionic liquids) for the recovery of microbial-based astaxanthin from microalgae (such as Haematococcus pluvialis) and yeast (such as Phaffia rhodozyma) cells. The principal advances in the area, process bottlenecks, solvent selection and strategies to improve the recovery of microbial astaxanthin are emphasized. The promising recovery yields using these environmentally friendly procedures in lab-scale are good indications and directions for their effective use in biotechnological processes for the production of commercial feed and food ingredients like astaxanthin.

Insights into chitosan-based cellulose nanowhiskers reinforced nanocomposite material via deep eutectic solvent in green chemistry.

In the present work, the synthesis of cellulose nanowhiskers (CNW)/chitosan nanocomposite films via deep eutectic solvents (DES) changing the chemical structures were carried out. It was observed that a pure chitosan film has broadband at 3180-3400 cm-1, indicating amide and hydroxyl groups. Upon CNW incorporation, the peak gets sharper and stronger and shifts to a greater wavelength. Further, the addition of DES infuses more elements of amide into the nanocomposite films. Moreover, the mechanical properties incorporating CNW filler into a chitosan matrix show an enhancement in tensile strength (TS), Young's modulus (YM), and elongation at break. The TS and YM increase while the elongation decrease as the CNW concentration increases. The YM of biocomposite films is increased to 723 MPa at 25% CNW into chitosan films. Besides, the TS has enhanced to 11.48 MPa at 15% CNW concentration in the biocomposite films. The elongation at break has decreased to 11.7% at 25% CNW concentration. Hence, incorporating CNW into the chitosan matrix via DES can still improve the mechanical properties of the nanocomposite films. Therefore, the application of DES results in a lower YM and TS as the films are hygroscopic. In conclusion, DES can be considered the new green solvent media for synthesizing materials. It has the potential to replace ionic liquids due to its biodegradability and non-toxic properties while preserving the character of low-vapour pressure. Besides that, chitosan can be used as potential material for applications in process industries, such as the biomedical and pharmaceutical industries. Thus, DES can be used as a green solvent and aim to reduce the toxic effect of chemicals on the environment during chemical production.

Combining environmental, health, and safety features with a conductor like Screening Model for selecting green solvents for antibiotic analyses.

Extraction and chromatographic techniques for analyzing pharmaceutically active compounds necessitate large quantities of organic solvents, resulting in a high volume of hazardous waste. The concept of green solvents focuses on protecting the environment by reducing or even eliminating the use of toxic solvents. The main objective of this critical review article is to build a framework for choosing green solvents for antibiotic analyses. The article briefly discusses the chemical properties of ciprofloxacin, sulfamethoxazole, tetracycline, and trimethoprim, and the current state of methodologies for their analyses in water and wastewater. It evaluates the greenness of solvents used for antibiotic analyses and includes insights on the comparison between conventional and green solvents for the analyses. An economic and environmental health and safety analysis combined with a Conductor-like Screening Model for Real Solvent (COSMO-RS) molecular simulation technique for predicting extraction efficiency was used in the evaluation. Methyl acetate and propylene carbonate tied for the greenest solvents from an environmental and economic perspective, whereas the COSMO-RS approach suggests dimethyl sulfoxide (DMSO) as the most suitable candidate. Although DMSO ranked third environmentally and economically, after methyl acetate and propylene carbonate, it would be an ideal replacement of hazardous solvents if it could be manufactured at a lower cost. DMSO showed the highest extraction capacity, as it can interact with antibiotics through hydrophobic interaction and hydrogen bonding. This article can be used as a green solvent selection guide for developing sustainable processes for antibiotic analyses.