A simple and efficient sample preparation for taxanes in Taxus chinensis needles with natural menthol-based aqueous deep eutectic solvent.

Taxanes are natural anticancer constituents, and the sample preparation from matrix normally depends on organochlorine solvents. In this study, green and natural menthol-based aqueous deep eutectic solvent was synthesized and used for sample preparation for taxanes. Five key parameters were optimized and the optimal preparation conditions were as follows: menthol/1-propanol ratio 1:1 (mol/mol), solid-liquid ratio 1:30 g/mL, extraction time 30 min, ultrasonic power 250 W, and water content 80%. Under the above conditions, the total extraction efficiency of seven main taxanes was 1.25- to 1.44-fold to the conventional methods. In addition, a high-performance liquid chromatography method with C18 column was established for quantitation of seven main taxanes in <25 min, which had excellent linearity (R2  > 0.9986), precision (relative standard deviation < 3.00%), repeatability (relative standard deviation < 3.69%), and recovery (90.26-109.00%). This method performed the extraction, and enrichment processes simultaneously, and it had advantages such as high extraction efficiency, simple operation, low cost, and eco-friendliness. This work indicated that the natural menthol-based deep eutectic solvent aqueous could be an excellent alternative to the sample preparation from Taxus or other plants.

Deep eutectic solvent functionalized graphene oxide composite adsorbent for miniaturized pipette-tip solid-phase extraction of toluene and xylene exposure biomarkers in urine prior to their determination with HPLC-UV.

A deep eutectic solvent functionalized graphene oxide composite adsorbent (DFG) was synthesized through reversible-addition fragmentation chain-transfer polymerization. The synthesized DFG had multiple adsorption interactions after covalent modification with a deep eutectic solvent (allyltriethylammonium bromide/ethylene glycol). Adsorption isotherms and kinetics studies of DFG indicate that the adsorption of hippuric acid (HA) and methylhippuric acid (MHA) was monolayer chemical adsorption. The comparison of DFG with commercial adsorbents demonstrates that the adsorption ability of DFG was superior. This was due to the multiple adsorption interactions of DFG for the three analytes (mainly π-interaction, hydrogen bonding, electrostatic adsorption, and hydrophobic interaction). The DFG adsorbent was applied to miniaturized pipette-tip solid-phase extraction (MPT-SPE), followed by high-performance liquid chromatography (HPLC) to determine biomarkers in urine for toluene and xylene exposure. The DFG-MPT-SPE-HPLC method required only 2.00 mg of DFG as adsorbent, 0.50 mL of washing solvent, and 0.40 mL of elution solvent to achieve a wide linear range (0.200-200 µg mL-1), high recoveries (90.9-99.1%), and high precision (RSD ≤ 6.3%). The proposed method was applied to determine HA and MHA in urine samples from occupational workers. Graphical abstract Deep eutectic solvent functionalized graphene oxide composite adsorbent for miniaturized pipette-tip solid-phase extraction of toluene and xylene exposure biomarkers in urine prior to their determination with HPLC-UV.

Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2-Hydroxyphenylbenzimidazole-based Scaffolds en Route to Donepezil-Like Compounds.

An unsubstituted 2-hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi-target ligand in Alzheimer's disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so-called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio-renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2-hydroxyphenylbenzimidazole-based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure-activity relationships (SARs).

Bio-Based Solvents and Gasoline Components From Renewable 2,3-Butanediol and 1,2-Propanediol: Synthesis and Characterization.

In this study approaches for chemical conversions of the renewable compounds 1,2-propanediol (1,2-PD) and 2,3-butanediol (2,3-BD) that yield the corresponding cyclic ketals and glycol ethers have been investigated experimentally. The characterization of the obtained products as potential green solvents and gasoline components is discussed. Cyclic ketals have been obtained by the direct reaction of the diols with lower aliphatic ketones (1,2-PD + acetone → 2,2,4-trimethyl-1,3-dioxolane (TMD) and 2,3-BD + butanone-2 → 2-ethyl-2,4,5-trimethyl-1,3-dioxolane (ETMD)), for which the ΔH0r, ΔS0r and ΔG0r values have been estimated experimentally. The monoethers of diols could be obtained through either hydrogenolysis of the pure ketals or from the ketone and the diol via reductive alkylation. In the both reactions, the cyclic ketals (TMD and ETMD) have been hydrogenated in nearly quantitative yields to the corresponding isopropoxypropanols (IPP) and 3-sec-butoxy-2-butanol (SBB) under mild conditions (T = 120-140 °C, p(H2) = 40 bar) with high selectivity (>93%). Four products (TMD, ETMD, IPP and SBB) have been characterized as far as their physical properties are concerned (density, melting/boiling points, viscosity, calorific value, evaporation rate, Antoine equation coefficients), as well as their solvent ones (Kamlet-Taft solvatochromic parameters, miscibility, and polymer solubilization). In the investigation of gasoline blending properties, TMD, ETMD, IPP and SBB have shown remarkable antiknock performance with blending antiknock indices of 95.2, 92.7, 99.2 and 99.7 points, respectively.

Effect of Four Novel Bio-Based DES (Deep Eutectic Solvents) on Hardwood Fractionation.

Using the basic principle of construction between a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD), four bio-based deep eutectic solvents (DESs) were prepared in a 1:2 molar ratio of HBA:HBD. 2,3-Dihydroxypropyl-1-triethylammonium chloride ([C9H22N+O2]Cl-) was synthesized from raw glycerol and used as an HBA. Lactic acid, urea, pure glycerol, and ethylene glycol were selected as HBD. Attempts to prepare DESs, using citric acid and benzoic acid as HBDs, were unsuccessful. All these DESs were characterized using FTIR and NMR techniques. Besides, physicochemical parameters such as pH, viscosity, density, and melting point were determined. The behavior of these DES to fractionate olive pomace was studied. Lignin recovery yields spanned between 27% and 39% (w/w) of the available lignin in olive pomace. The best DES, in terms of lignin yield ([C9H22N+O2]Cl- -lactic acid), was selected to perform a scale-up lignin extraction using 40 g of olive pomace. Lignin recovery on the multigram scale was similar to the mg scale (38% w/w). Similarly, for the holocellulose-rich fractions, recovery yields were 34% and 45% for mg and multi-gram scale, respectively. Finally, this DES was used to fractionate four fruit pruning samples. These results show that our novel DESs are alternative approaches to the ionic liquid:triethylammonium hydrogen sulfate and the widely used DES: choline chloride:lactic acid (1:10 molar ratio) for biomass processing.

Deep eutectic solvents for pharmaceutical formulation and drug delivery applications.

Solvents play key roles in designing drug delivery systems (DDSs). They are used as the reaction media in the preparation of DDSs and as vehicles for delivery of problematic drugs. The number of pharmaceutically acceptable solvents is limited and developing new green ones is of a great of interest. A deep eutectic solvent (DES) is a room temperature liquid composed of a mixture of hydrogen bond acceptor and hydrogen bond donor. DESs exhibit interesting physical and chemical characteristics such as low vapor pressure, non-inflammability, chemically tailorable, solvency power for a wide range of solutes, and water non-reactivity. Furthermore, they can be easily prepared from low toxicity, readily available, and inexpensive constituents. Due to these properties, DESs have attracted growing attention as green solvents in different areas of science from chemistry to material engineering and biology. In this review, after a brief introduction about DESs, we provide an overview about current advances made over the last decade in utilizing of DESs for solubilization of water insoluble drugs, transdermal drug delivery, inorganic nanoparticle synthesis, and designing polymeric and self-assembled drug carriers. This paper also discusses main challenges and limitations of DESs that should be considered before using of them.

Preparation of two-dimensional magnetic molecularly imprinted polymers based on boron nitride and a deep eutectic solvent for the selective recognition of flavonoids.

New types of two-dimensional (2D) boron nitride (BN) were developed as a 2D scaffold material. After modification with ternary deep eutectic solvents (DES, ChCl-caffeic acid-ethylene glycol), the processed BN was applied to the preparation of magnetic molecularly imprinted polymers (MMIPs). In the polymerization of MMIPs, DESs and hydrophobic Fe3O4 magnetite were applied as the functional monomer and magnetically susceptible component, respectively. A 2D ellipsoid material was formed successfully by polymerization on the surface of the processed BN. The proposed 2D-MMIPs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and nitrogen sorption analysis techniques. The surface area of the 2D-MMIPs was increased using eco-friendly chemicals. The proposed 2D-MMIPs had a 2D oblate structure and a large surface area. The 2D-MMIPs were used for the preconcentration of flavonoids from Ginkgo biloba leaf extracts. High performance liquid chromatography-ultraviolet analysis revealed that the 2D-MMIPs have higher recoveries for the flavonoids (quercetin 96.8%, isorhamnetin 93.6% and kaempferol 94.8%) in Ginkgo biloba leaves than common MMIPs.

Cyclobutane-Containing Scaffolds as Useful Intermediates in the Stereoselective Synthesis of Suitable Candidates for Biomedical Purposes: Surfactants, Gelators and Metal Cation Ligands.

Efficient and versatile synthetic methodologies are reported for the preparation of products that are suitable candidates to be used as surfactants, gelators for hydroxylic solvents or metal cation ligands, with potential use in several fields including biomedical applications. The common structural feature of all the synthesized products is the presence of a cis or trans-1,2- or cis-1,3-difunctionalized cyclobutane ring. In the two first cases, the key intermediates including enantiomerically pure 1,3-diamines and 1,3-amino alcohols have been prepared from ß-amino acid derivatives obtained, in turn, from a chiral half-ester. This compound is also precursor of γ-amino esters. Furthermore, two kind of polydentate ligands have also been synthesized from a symmetric 1,5-diamine obtained from norpinic acid, which was easily prepared from commercial verbenone.

Manufacturing of Multi-drug Formulations with Customised Dose by Solvent Impregnation of Mesoporous Silica Tablets.

The manufacture of personalised medicines where specific combinations of active pharmaceutical ingredients (APIs) and their dose within a tablet would be adjusted to the needs of individual patients, would require new manufacturing approaches compared to the established practice. In the case of low-dose formulations, the required precision of API content might not be achievable by traditional unit operations such as solid powder blending. The aim of the present work was to explore an alternative approach, based on the concept of pre-formulated placebo tablets containing mesoporous silica particles capable of absorbing APIs in the form of solutions, which can be precisely dosed at arbitrarily low quantities. The precision of the liquid dosing system has been validated; it was shown that the mechanical properties of the tablets were satisfactory even after multiple impregnation-drying cycles and that pharmacopoeia specifications on content uniformity could be met. Using model APIs, the spatial distribution of the API within the tablet after impregnation was investigated and shown to depend on the number and order of the impregnation-drying cycles. It was found that when an API was loaded to the tablet in a single step, a different dissolution profile was obtained compared to the same quantity dosed in multiple smaller steps. Overall, the approach of loading multiple API to a pre-formulated tablet at defined quantities using drop-on-demand liquid dosing was found to be feasible from the dose uniformity point of view. Further research should focus on potential API interactions and storage stability of tablets manufactured in this way.

High-Throughput Analysis for Artemisinins with Deep Eutectic Solvents Mechanochemical Extraction and Direct Analysis in Real Time Mass Spectrometry.

A fast, simple, efficient, and high-throughput analytical protocol using deep eutectic solvents (DES) for mechanochemical extraction (MCE) combined with direct analysis in real time mass spectrometry (DART-MS) was developed to quantify heat-labile bioactive compounds artemisinin (AN), arteannuin B, and artemisinic acid from Aretemisia annua. MCE is performed at room temperature, and target analytes are released into DESs within seconds; this method demonstrated multiple advantages over traditional extraction methods and organic solvents. DART-MS was then used for the structure confirmation and quantification for the three artemisinin major components extracted from plants of five locations. Liquid chromatography (LC) measurements were performed as well for results verification and comparison, and the amounts obtained were consistent between the two techniques. DART-MS showed advantages in simplicity, low limit of detection (5-15 ng mL-1), and superior speed (10-20 s), but with slightly higher relative standard deviation (0.7-10.8%). The entire protocol can be accomplished in a few minutes from raw materials to quantitative results. This study aims to establish a methodology combining high-efficiency sample pretreatment and rapid chemical analysis from complex matrixes, where the time-consuming separation procedure can be eliminated. Additionally, the use of toxic organic solvents needed in the process of chemical extraction and analysis is largely avoided. In general, this investigation provides a robust analytical procedure that can be widely used in many areas of research and industrial activities.

A new strategy for accelerated extraction of target compounds using molecularly imprinted polymer particles embedded in a paper-based disk.

In this study, a general simple and inexpensive method is introduced for the preparation of a paper-based selective disk-type solid phase extraction (SPE) technique, appropriate for fast and high throughput monitoring of target compounds. An ion exchange molecularly imprinted polymer (MIP) was synthesized for the extraction and analysis of acesulfame, an anthropogenic water quality marker. Acesulfame imprinting was used as an example for demonstrating the benefits of a nanosized, swellable MIP extraction sorbents integrated in an on-site compatible concept for water quality monitoring. Compared with an 8 mL standard SPE cartridge, the paper-based MIP disk (47 mm ø) format allowed (1) high sample flow rates up to 30 mL•min-1 without losing extraction efficiency (2) extracting sample volumes up to 500 mL in much shorter times than with standard SPE, (3) the reuse of the disks (up to 3 times more than SPE cartridge) due to high robustness and an efficient post-cleaning, and (4) reducing the sampling time from 100 minutes (using the standard SPE format) to about 2 minutes with the MIP paper disk for 50 mL water sample. Different parameters like cellulose fiber/polymer ratios, sample volume, sample flow-rate, washing, and elution conditions were evaluated and optimized. Using developed extraction technique with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis, a new protocol was established that provides detection and quantification limits of 0.015 µg•L-1 and 0.05 µg•L-1 , respectively. The developed paper disks were used in-field for the selective extraction of target compounds and transferred to the laboratory for further analysis.

Macroscopic Supramolecular Assembly through Electrostatic Interactions Based on a Flexible Spacing Coating.

Macroscopic supramolecular assembly (MSA) is a recent advance in supramolecular chemistry that involves associating large building blocks with a size larger than 10 µm through noncovalent interactions. However, until now the applicable material system is rather limited to hydrogels, and MSA of rigid materials with supramolecular interactions widely used in molecular assembly has rarely been reported due to the difficulty in achieving multivalency between rigid surfaces. Herein, the concept of flexible spacing coating is applied with highly flowable properties, and the electrostatic-interaction-driven MSA of relatively rigid polydimethylsiloxane building blocks is demonstrated. With the flexible spacing coating of a polyelectrolyte multilayer, the oppositely charged rigid building blocks can realize MSA under shaking in water for 5 min. The major contribution of the electrostatic interaction is confirmed by both qualitative controlled MSA experiments in other solvents, disassembly in ionic solution and quantitative results with an in situ force measurement method.

Injectable sustained release PLA microparticles prepared by solvent evaporation-media milling technology.

The objective of this study was to develop agomelatine (AGM) intramuscular sustained release PLA microparticles by using solvent evaporation combined with wet milling technology. The final preparation had a regular and homogeneous particle size of approximately 35 µm, as measured by laser diffraction particle size analysis and scanning electron microscopy (SEM). The drug was confirmed to be within the carrier in an amorphous state through differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD) experiments. Additionally, Fourier transform infrared spectroscopy (FT-IR) analysis was applied to confirm that there was hydrogen bonding between the drug and polymer at the molecular level. In vitro release experiments indicated that the drug could achieve long-term sustained release over the period of one month, with only a 3.07% burst release, due to the involvement of the polymer and removal of drug adsorbed on the surface during the wet grinding process. The dominant release mechanism was considered to be diffusion of the drugs in the initial period. Following this, with the hydrolysis of PLA to form a colloidal viscous layer, drug release is due to the combined effect of diffusion and erosion of the polymer matrix. Additionally, drug release behavior is closely related to the degradation mechanism of the polymer carrier. The results suggest that AGM could be developed as a potential delivery system for long-acting intramuscular administration with extensive application prospects.

Agglomeration of celecoxib by quasi-emulsion solvent diffusion method without stabilizer: effect of good solvent.

AIM: The aim of the present research is to investigate the feasibility of agglomeration of crystals by the quasi-emulsion solvent diffusion method without using a stabilizer. METHOD: Two solvent systems comprising a solvent and an antisolvent (water) were used to prepare celecoxib agglomerates. To this end, seven solvents including propanol, methyl acetate, methyl ethyl ketone, butanol, ethyl acetate, isopropyl acetate, and pentanol were examined. The agglomerates were evaluated by micromeritic properties (e.g., size, density, flowability), yield, drug physical state, friability, and dissolution behavior. RESULTS: In the present study the clear trend was observed experimentally in the agglomerate properties as a function of physical properties of the solvent such as miscibility with water. Solvents with high water miscibility (25% v/v) resulted in sticky and hollow particles, while solvents with low water miscibility (3%v/v) led to the formation of agglomerates with low strength. However, the agglomerates made from the solvents with intermediate water miscibility (10% v/v), may reflect a greater integrity of the agglomerates regarding yield and strength. CONCLUSION: Results of this study offer a useful starting point for a conceptual framework to guide the selection of solvent systems for the quasi-emulsion solvent diffusion method without using a stabilizer.

Characterization of Inclusion Complex of Coenzyme Q10 with the New Carrier CD-MOF-1 Prepared by Solvent Evaporation.

The aim of the current study was to evaluate the physicochemical properties of a solid dispersion of coenzyme Q10 (CoQ10)/cyclodextrin metal organic frameworks-1 (CD-MOF-1). As a result of the powder X-ray diffraction (PXRD), it was confirmed that the CD-MOF-1 was changed from the α form to the ß form by evaporation (EVP). A diffraction peak due to melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). The structure of this complex is presumed to be similar to the ß form of CD-MOF-1. As a result of the differential scanning calorimetry (DSC), the endothermic peak due to the melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). As a result of the near-infrared (NIR) absorption spectroscopy, findings suggested the hydrogen bond in formation between the CH group in the isoprene side chains of CoQ10 and the OH group of CD-MOF-1. Therefore, the formation of crystal solid dispersion in CoQ10/CD-MOF-1 was suggested. As a result of the dissolution test in distilled water, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in comparison to CoQ10 alone. Furthermore, also in fasted state simulated intestinal fluid (FaSSIF) in vivo, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in the human body than CoQ10 alone. From the results of 2D-nuclear overhauser effect spectroscopy (NOESY) NMR spectroscopy, CD-MOF-1 could not include the benzoquinone ring of CoQ10. It was confirmed that the isoprene side chain was included. Therefore, it was suggested that CD-MOF-1 useful as a novel drug carrier for CoQ10.

SET-LRP in the Neoteric Ethyl Lactate Alcohol.

Ethyl lactate (EtLa), a green and safe agrochemical solvent, is gifted with some properties that make it a good candidate for SET-LRP. It dissolves CuBr2, mediates an efficient disproportionation of CuBr in the presence of tris(2-(dimethylamino)ethyl)amine (Me6-TREN), and is capable to dissolve both aqueous (polar) and hydrocarbon (nonpolar) soluble monomers and polymers. Here, we report that EtLa is an excellent solvent for the Cu(0) wire-catalyzed SET-LRP to produce both hydrophilic and hydrophobic polyacrylates that exhibit precise chain end functionality. These results will expand the table of SET-LRP solvents with a new green member of biological origin that is also biodegradable and, therefore, are expected to contribute to continue expanding the use of SET-LRP in the field of biomacromolecules, bioconjugates, and other biology and medicine related disciplines.

Challenges in the development of bio-based solvents: a case study on methyl(2,2-dimethyl-1,3-dioxolan-4-yl)methyl carbonate as an alternative aprotic solvent.

Many traditional solvents have drawbacks including sustainability and toxicity issues. Legislation, such as REACH, is driving the move towards less hazardous chemicals and production processes. Therefore, safer bio-based solvents need to be developed. Herein, a 10 step method has been proposed for the development of new bio-based solvents, which utilises a combination of in silico modelling of Hansen solubility parameters (HSPs), experimental Kamlet-Abboud-Taft parameters, a selection of green synthetic routes followed by application testing and toxicity measurements. The challenges that the chemical industry face in the development of new bio-based solvents are highlighted through a case study on methyl(2,2-dimethyl-1,3-dioxolan-4-yl)methyl carbonate (MMC), which can be synthesised from glycerol. Although MMC is an attractive candidate as a replacement solvent, simply being bio-derived is not enough for a molecule to be regarded as green. The methodology of solvent development described here is a broadly applicable protocol that will indicate if a new bio-based solvent is functionally proficient, and will also highlight the importance of early stage Kamlet-Abboud-Taft parameters determination and toxicity testing in the development of a green solvent.

The use of dimethylsulfoxide as a solvent in enzyme inhibition studies: the case of aldose reductase.

Aldose reductase (AR) is an enzyme devoted to cell detoxification and at the same time is strongly involved in the aetiology of secondary diabetic complications and the amplification of inflammatory phenomena. AR is subjected to intense inhibition studies and dimethyl sulfoxide (DMSO) is often present in the assay mixture to keep the inhibitors in solution. DMSO was revealed to act as a weak but well detectable AR differential inhibitor, acting as a competitive inhibitor of the L-idose reduction, as a mixed type of non-competitive inhibitor of HNE reduction and being inactive towards 3-glutathionyl-4-hydroxynonanal transformation. A kinetic model of DMSO action with respect to differently acting inhibitors was analysed. Three AR inhibitors, namely the flavonoids neohesperidin dihydrochalcone, rutin and phloretin, were used to evaluate the effects of DMSO on the inhibition studies on the reduction of L-idose and HNE.

A pre-formulation study of a polymeric solid dispersion of paclitaxel prepared using a quasi-emulsion solvent diffusion method to improve the oral bioavailability in rats.

OBJECTIVE: To preliminarily develop a surfactant-free, polymeric solid dispersion (PSD) of paclitaxel suitable for oral administration. METHODS: A co-solvent quench method was applied to screen the proper polymer matrix of the PSD which were prepared in a liquid system using a quasi-emulsion solvent diffusion method (QESDM). Three dissolution experiments and two in vivo tests in rats were used to explain the differences among the formulations. RESULTS: The theoretical solubility ratio of amorphous/crystalline PTX was 92.6 (37 °C). Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was chosen as the polymer carrier of the PSD and a porous silicon dioxide [called white carbon black (WCB)] was selectable to be used to further adjust the dissolution rate. The absolute oral bioavailability (AOB, 20 mg/kg) of the three formulas [HPMCAS/paclitaxel/WCB = 4/1/0 (F1), 8/1/0 (F2) and 4/1/4 (F3), w/w/w] were 11.8, 13.6 and 25.6%, respectively. The AOB of F3 is nearly seven times higher than that (3.8%) of paclitaxel material (a control). The advantage of higher HPMCAS/paclitaxel ratio of F2 in a dissolution test was not reflected in the first in vivo test due to the relatively higher dose of polymer which could not be effectively dissolved under the limitation of intestinal environment. This was deduced from the dissolution tests and was finally validated when the oral dose of PTX (and thus polymer) was reduced. The relevant AOBs (10 mg/kg) were 10.4, 20.8 and 19.6%, respectively. CONCLUSION: The PSD is a promising formulation strategy and the QESDM is a practical preparation method to implement such formulation design.

Special Issue: "Organic Reactions in Green Solvents".

To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of a safe, non-toxic, biorenewable and cheap reaction media is a crucial goal in organic synthesis. Thus, this Special Issue on "Organic Reactions in Green Solvents" has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of organic synthesis in Green Solvents (ranging from metal- to organo-catalyzed organic reactions).