Carbon Dots: A Review with Focus on Sustainability.

Carbon dots (CDs) are an emerging class of nanomaterials with attractive optical properties, which promise to enable a variety of applications. An important and timely question is whether CDs can become a functional and sustainable alternative to incumbent optical nanomaterials, notably inorganic quantum dots. Herein, the current CD literature is comprehensively reviewed as regards to their synthesis and function, with a focus on sustainability aspects. The study quantifies why it is attractive that CDs can be synthesized with biomass as the sole starting material and be free from toxic and precious metals and critical raw materials. It further describes and analyzes employed pretreatment, chemical-conversion, purification, and processing procedures, and highlights current issues with the usage of solvents, the energy and material efficiency, and the safety and waste management. It is specially shown that many reported synthesis and processing methods are concerningly wasteful with the utilization of non-sustainable solvents and energy. It is finally recommended that future studies should explicitly consider and discuss the environmental influence of the selected starting material, solvents, and generated byproducts, and that quantitative information on the required amounts of solvents, consumables, and energy should be provided to enable an evaluation of the presented methods in an upscaled sustainability context.

A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates.

The Heck reaction is widely employed to build a variety of biologically relevant scaffolds and has been successfully implemented in the production of active pharmaceutical ingredients (APIs). Typically, the reaction with terminal alkenes gives high yields and stereoselectivity toward the trans-substituted alkenes product, and many green variants of the original protocol have been developed for such substrates. However, these methodologies may not be applied with the same efficiency to reactions with challenging substrates, such as internal olefins, providing trisubstituted alkenes. In the present work, we have implemented a Heck reaction protocol under green conditions to access trisubstituted alkenes as final products or key intermediates of pharmaceutical interest. A set of preliminary experiments performed on a model reaction led to selecting a simple and green setup based on a design of experiments (DoE) study. In such a way, the best experimental conditions (catalyst loading, equivalents of alkene, base and tetraalkylammonium salt, composition, and amount of solvent) have been identified. Then, a second set of experiments were performed, bringing the reaction to completion and considering additional factors. The protocol thus defined involves using EtOH as the solvent, microwave (mw) irradiation to achieve short reaction times, and the supported catalyst Pd EnCat®40, which affords an easier recovery and reuse. These conditions were tested on different aryl bromides and internal olefines to evaluate the substrate scope. Furthermore, with the aim to limit as much as possible the production of waste, a simple isomerization procedure was developed to convert the isomeric byproducts into the desired conjugated E alkene, which is also the thermodynamically favoured product. The approach herein disclosed represents a green, efficient, and easy-to-use handle towards different trisubstituted alkenes via the Heck reaction.

Advancing Green Chemistry in Antiviral Therapeutics: A Comprehensive Review.

Cytomegalovirus (CMV) is a prevalent virus across the world that belongs to the family Herpesviridae but remains dormant in the body unless the immune system is compromised. In addition, when the bacterium is compromised without any health risks, the infection spreads from one person to another person through body fluids, such as saliva, blood, etc. Ganciclovir is an anti- viral medication used in treating viral infections, especially in the treatment of CMV in people with acquired immune deficiency syndrome and immunity at risk. The quality control of ganciclovir in industries is carried out by using anti-green solvents in large volumes; these solvents are not safe in consideration of environmental factors and analysts. Also, the waste generation by these solvents causes hazardous effects on the environment. Further, using 12 green analytical chemistry principles promotes the awareness of analytical judgments among the research groups. It is a revolutionary step in the analytical field to enhance the safety of the environment, and analysts, apart from safety, help to control waste production and conserve energy-reducing occupational hazards. Many works have been carried out for the quality control of ganciclovir using different solvents, such as acetonitrile, methanol, etc. Despite this, there are no existing methods with green solvents or procedures to reduce energy and waste generation. Therefore, the purpose of this review is to understand the drug profile of ganciclovir and the methods developed.

Ultrasonic extraction of Inula viscosa: Enhancing antioxidant bioactivity and its application in sunflower oil as an antioxidant.

The objective of this study was to optimize the ultrasound-assisted extraction (UAE) of Inula viscosa, focusing on the extraction yield, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity and to evaluate its antioxidant effect in sunflower oil (SFO) storage. A water-ethanol binary solvent system was applied to extract bioactive components sustainably. Extraction parameters (temperature, time, ethanol concentration, and solvent-to-solid ratio) were optimized using a central composite rotatable design, achieving high accuracy (R2 > 0.974). Optimum conditions were 54 % (v/v) ethanol concentration, 60 °C, 31 min, and a 15 (mL/g) solvent-to-solid ratio resulting in a yield of 24.72 g/g (%), TPC of 489.54 mg gallic acid/g, TFC of 149.81 mg quercetin/g, and IC50 of 18.21 µg/mL. UAE outperformed Soxhlet extraction in yield, bioactive compound composition, and antioxidant capacity. Strong correlations were found between TPC, TFC, and antioxidant capacity, with TFC having a more significant impact. I. viscosa extract was found to be a potent antioxidant and delay the oxidation of SFO during accelerated storage due to peroxide value and oxidative induction time analysis. Microstructural analysis illuminated the structural changes induced by the extraction methods. In conclusion, this study not only optimized UAE of I.viscosa, showing superior efficiency and antioxidant capacity, but also demonstrated the practical application of I.viscosa in enhancing sunflower oil shelf life, thereby providing valuable insights for the field of food engineering and antioxidant research.

Pathways to Upscaling Highly Efficient Organic Solar Cells Using Green Solvents: A Study on Device Photophysics in the Transition from Lab-to-Fab.

As the rise of nonfullerene acceptors (NFA) has allowed lab-scale organic solar cells (OSC) to reach 20% efficiency, translating these devices into roll-to-roll compatible fabrication still poses many challenges for researchers. Among these are the use of green solvent solubility for large-scale manufacture, roll-to-roll compatible fabrication, and, not least, information on charge carrier dynamics in each upscaling step, to further understand the gap in performance. In this work, the reproducibility of champion devices using slot-die coating with 14% power conversion efficiency (PCE) is demonstrated, under the condition that the optimal thickness is maintained. It is further shown that for the donor:acceptor (D:A) blend PM6:Y12, the processing solvent has a more significant impact on charge carrier dynamics compared to the deposition technique. It is found that the devices processed with o-xylene feature a 40% decrease in the bimolecular recombination coefficient compared to those processed with CB, as well as a 70% increase in effective mobility. Finally, it is highlighted that blade-coating yields devices with similar carrier dynamics to slot-die coating, making it the optimal choice for lab-scale optimization with no significant loss in translation toward up-scale.

Exploring hydrodynamic cavitation for citrus waste valorisation in Malta: from beverage enhancement to potato sprouting suppression and water remediation.

Introduction: The endorsement of circular economy, zero-waste, and sustainable development by the EU and UN has promoted non-thermal technologies in agro-food and health industries. While northern European countries rapidly integrate these technologies, their implementation in Mediterranean food-supply chains remains uncertain. Aims: We evaluated the usefulness of hydrodynamic cavitation (HC) for valorizing orange peel waste in the fresh orange juice supply chain of the Maltese Islands. Method: We assessed: a) the effectiveness of HC in extracting bioactive compounds from orange peels (Citrus sinensis) in water (35°C) and 70% (v/v) ethanol (-10°C) over time, compared to conventional maceration, and b) the potato sprouting-suppression and biosorbent potential of the processed peel for copper, nitrate, and nitrite binding. Results: Prolonged HC-assisted extractions in water (high cavitation numbers), damaged and/or oxidized bioactive compounds, with flavonoids and ascorbic acid being more sensitive, whereas cold ethanolic extractions preserved the compounds involved in radical scavenging. HC-processing adequately modified the peel, enabling its use as a potato suppressant and biosorbent for copper, nitrate, and nitrite. Conclusion: Coupling HC-assisted bioactive compound extractions with using leftover peel for potato-sprouting prevention and as biosorbent for water pollutant removal offers a straightforward approach to promoting circular economic practices and sustainable agriculture in Malta.

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.

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.

Optimizing ultrasound-assisted extraction of bioactive compounds from Canthium horridum blume leaves utilizing polyols: A study on skin-related activities.

The focus on reducing organic solvent usage, owing to their negative environmental and health impacts, is driving a search for innovative green alternative solvents in academia and industry. Canthium horridum Blume (CH) exhibits many therapeutic activities, including antioxidant and anti-inflammatory efficacy. The objective of this study is to evaluate the optimal solvent concentration using a simplex-lattice design with an aqueous-polyols mixture and to optimize the parameters for extracting bioactive compounds and antioxidant activities from ultrasound-assisted extraction (UAE) of CH leaves through central composite design (CCD) in response surface methodology (RSM). This study examines the total phenolic content (TPC), antioxidant activities, comparison of different extraction conditions, identification of bioactive compounds, cell cytotoxicity, cellular antioxidant activity, and melanin content reduction efficacy of the extracts. According to the findings from the simplex-lattice model, the ideal solvent composition consisted of 32.57%w/w butylene glycol, 32.92%w/w glycerine, and 34.51%w/w water. Furthermore, based on the response model, optimal extraction conditions were identified as a 15-min extraction time and a solvent-to-sample ratio of 32.94:1. In comparison to alternative extraction methods, ultrasonic-assisted extraction using the aqueous-glycerine-butylene glycol (GB-UAE) extract resulted in notably elevated TPC and antioxidant responses (p < 0.05). Major antioxidant bioactive compounds included 4-(Butoxymethyl) phenol, 3-O-Caffeoyl-4-O-methylquinic acid, Quercetin 3-(2G-glucosylrutinoside), 2,4-Dihydroxybenzoic acid and other bioactive compounds. The GB-UAE extract revealed greater cell viability than UAE using ethanol (EtOH-UAE) extract in both cytotoxicity and cellular antioxidant assays at the same concentration. Additionally, it exhibited comparable melanin content reduction efficacy at a higher concentration compared to that of EtOH-UAE extract. The researcher anticipates that the current study will advance the utilization of an aqueous-polyols system for extracting bioactive compounds extending beyond CH leaves. Although the potential applications of CH leaves in cosmetics and pharmaceutical formulations have been identified, further comprehensive mechanistic and clinical studies are required to fully understand their effects.

Tuning Local Order in Starch Nanoparticles Exploiting Nonsolvency with "Green" Solvents.

Starch is a renewable biopolymer that can be sourced from agricultural waste and used to produce nanoparticles (SNPs). In particular, amorphous SNPs have potential application in numerous fields, including the consolidation of weakened paintings in the cultural heritage preservation. Starch dissolution followed by nanoprecipitation in nonsolvents is an advantageous synthetic route, but new methodologies are needed to feasibly control the physicochemical properties of the SNPs. Here, we explored nanoprecipitation by nonsolvency using a set of "green" solvents to obtain amorphous SNPs, rather than starch nanocrystals already reported in the literature. The effect of the nonsolvent on the ordering of polymer chains in the obtained SNPs was studied. The recovery of local order (e.g., isolated V-type helices) after dissolution was shown to depend on the type of solvents used in the dissolution and precipitation steps, while long-range order (extended arrays of helices) is lost. Aqueous dispersions of the SNPs provided effective consolidation of powdery painted layers, showing that the selection of particle synthetic routes can be dictated by sustainability and scalability criteria. These "green" formulations are candidates as new consolidants in art preservation, and the possibility of tuning local order in amorphous starch assemblies might also impact fields like food chemistry, pharmaceutics, and nanocomposites, where SNPs with tunable amorphousness are more advantageous than nanocrystals.

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.

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.

Sustainable extraction methods of carotenoids from mango (Mangifera indica L. 'Kent') pulp: Ultrasound assisted extraction and green solvents.

Mango is a good source of carotenoids for use in food, cosmetic, and pharmaceutical products because of their organoleptic and health-promoting properties. Safe and sustainable methods for their extraction is required. The present investigation was aimed to study concentration and carotenoid profile of 'Kent' mango pulp through a conventional extraction (CE) and ultrasound-assisted extraction (UAE) using traditional solvents (tetrahydrofuran-THF and diethyl ether: petroleum ether-DE:PE) and green solvents (GS) (2-metiltetrahydrofuran, 2 m-THF; cyclopentyl methyl ether, CPME). Mango showed (µg/g d.w.) ß-carotene (29.4), zeaxanthin (1.28), ß-cryptoxanthin (2.8), phytoene (18.68) and phytofluene (7.45) in a CE using DE:PE. Similar results were obtained applying DE:PE in UAE and GS in a CE, so CPME and 2-mTHF seem suitable solvents to replace DE:PE in CE. The yield of total carotenes, xanthophylls and carotenoids using GS combined with UAE was lower than with CE, but important enough to be used as a sustainable procedure for obtaining carotenoids from mango pulp.

Polyhydroxyalkanoate recovery overview: properties, characterizations, and extraction strategies.

Due to their excellent properties, polyhydroxyalkanoates are gaining increasing recognition in the biodegradable polymer market. These biogenic polyesters are characterized by high biodegradability in multiple environments, overcoming the limitation of composting plants only and their versatility in production. The most consolidated techniques in the literature or the reference legislation for the physical, chemical and mechanical characterisation of the final product are reported since its usability on the market is still linked to its quality, including the biodegradability certificate. This versatility makes polyhydroxyalkanoates a promising prospect with the potential to replace fossil-based thermoplastics sustainably. This review analyses and compares the physical, chemical and mechanical properties of poly-ß-hydroxybutyrate and poly-ß-hydroxybutyrate-co-ß-hydroxyvalerate, indicating their current limitations and strengths. In particular, the copolymer is characterised by better performance in terms of crystallinity, hardness and workability. However, the knowledge in this area is still in its infancy, and the selling prices are too high (9-18 $ kg-1). An analysis of the main extraction techniques, established and in development, is also included. Solvent extraction is currently the most widely used method due to its efficiency and final product quality. In this context, the extraction phase of the biopolymer production process remains a major challenge due to its high costs and the need to use non-halogenated toxic solvents to improve the production of good-quality bioplastics. The review also discusses all fundamental parameters for optimising the process, such as solubility and temperature.

Green Solvents for Extraction of Natural Food Colorants from Plants: Selectivity and Stability Issues.

Consumers associate the color of food with its freshness and quality. More and more attention is being paid to natural colorants that bring additional health benefits to humans. Such natural substances are the carotenoids (yellow to orange), the anthocyanins (red to blue), and the betalains (red and yellow), which are very sensitive to exposure to light, air, high temperatures, and chemicals. Stability and diversity in terms of color can be optimized by using environmentally friendly and selective extraction processes that provide a balance between efficacy, safety, and stability of the resulting extracts. Green solvents like water, supercritical fluids, natural deep eutectic solvents, and ionic liquids are the most proper green solvents when combined with different extraction techniques like maceration, supercritical extraction, and ultrasound-assisted or microwave-assisted extraction. The choice of the right extracting agent is crucial for the selectivity of the extraction method and the stability of the prepared colorant. The present work reviews the green solvents used for the extraction of natural food colorants from plants and focuses on the issues related to the selectivity and stability of the products extracted.

A systematic review on green and natural polymeric nanofibers for biomedical applications.

Electrospinning is the simplest technique to produce ultrathin nanofibers, which enables the use of nanotechnology in various applications. Nanofibrous materials produced through electrospinning have garnered significant attention in biomedical applications due to their unique properties and versatile potential. In recent years, there has been a growing emphasis on incorporating sustainability principles into material design and production. However, electrospun nanofibers, owing to their reliance on solvents associated with significant drawbacks like toxicity, flammability, and disposal challenges, frequently fall short of meeting environmentally friendly standards. Due to the limited solvent choices and heightened concerns for safety and hygiene in modern living, it becomes imperative to carefully assess the implications of employing electrospun nanofibers in diverse applications and consumer products. This systematic review aims to comprehensively assess the current state of research and development in the field of "green and natural" electrospun polymer nanofibers as well as more fascinating and eco-friendly commercial techniques, solvent preferences, and other green routes that respect social and legal restrictions tailored for biomedical applications. We explore the utilization of biocompatible and biodegradable polymers sourced from renewable feedstocks, eco-friendly processing techniques, and the evaluation of environmental impacts. Our review highlights the potential of green and natural electrospun nanofibers to address sustainability concerns while meeting the demanding requirements of various biomedical applications, including tissue engineering, drug delivery, wound healing, and diagnostic platforms. We analyze the advantages, challenges, and future prospects of these materials, offering insights into the evolving landscape of environmentally responsible nanofiber technology in the biomedical field.

Designing Low Toxic Deep Eutectic Solvents for the Green Recycle of Lithium-Ion Batteries Cathodes.

The Lithium-ion battery (LIB) is one of the main energy storage equipment. Its cathode material contains Li, Co, and other valuable metals. Therefore, recycling spent LIBs can reduce environmental pollution and resource waste, which is significant for sustainable development. However, traditional metallurgical methods are not environmentally friendly, with high cost and environmental toxicity. Recently, the concept of green chemistry gives rise to environmental and efficient recycling technology, which promotes the transition of recycling solvents from organic solvents to green solvents represented by deep eutectic solvents (DESs). DESs are considered as ideal alternative solvents in extraction processes, attracting great attention due to their low cost, low toxicity, good biodegradability, and high extraction capacity. It is very important to develop the DESs system for LIBs recycling for sustainable development of energy and green economic development of recycling technology. In this work, the applications and research progress of DESs in LIBs recovery are reviewed, and the physicochemical properties such as viscosity, toxicity and regulatory properties are summarized and discussed. In particular, the toxicity data of DESs are collected and analyzed. Finally, the guidance and prospects for future research are put forward, aiming to explore more suitable DESs for recycling valuable metals in batteries.

Choline chloride-based deep eutectic solvents as plasticizer and active agent in chitosan films.

The growing concern over extending the shelf life of food products, coupled with the escalating environmental impact of synthetic plastic waste, has fuelled a quest for bio-based alternatives in packaging research. In response to this pressing need, our study delves into the synthesis of chitosan-based films incorporating a deep eutectic solvents (DES). Choline chloride and diverse hydrogen bond donors were used as plasticizers, we also explored the active properties of DES integrated into the chitosan (Ch) matrix. The Ch-based films with chlorine chloride: citric acid can prevent the mold spotting up to 29 days longer in comparison to bread wrapped in polyethylene films (PE). The obtained Ch/DES films exhibited mechanical properties comparable to conventional PE (e.g., up to tensile strength of 26 MPa and up to 210% in case of elongation at break). This synthesis approach represents a significant stride towards environmentally friendly packaging materials, aligning with the principles of green chemistry.

Recent Progress in Dopant-Free and Green Solvent-Processable Organic Hole Transport Materials for Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transport layers (HTLs) are crucial in enhancing perovskite solar cells (pero-SCs). Nevertheless, conventional processing of these HTL materials involves using toxic solvents, which gives rise to substantial environmental concerns and renders them unsuitable for large-scale industrial production. Consequently, there is a pressing need to develop dopant-free HTL materials processed using green solvents to facilitate the production of high-performance pero-SCs. Recently, several strategies have been developed to simultaneously improve the solubility of these materials and regulate molecular stacking for high hole mobility. In this review, a comprehensive overview of the methodologies utilized in developing dopant-free HTL materials processed from green solvents is provided. First, the study provides a brief overview of fundamental information about green solvents and Hansen solubility parameters, which can serve as a guideline for the molecular design of optimal HTL materials. Second, the intrinsic relationships between molecular structure, solubility in green solvents, molecular stacking, and device performance are discussed. Finally, conclusions and perspectives are presented along with the rational design of highly efficient, stable, and green solvent-processable dopant-free HTL materials.