Insights into the Nature of Eutectic and Deep Eutectic Mixtures

A stricter definition of a deep eutectic solvent (DES) is urgent, so that it may become a sound basis for further developments in this field. This communication aims at contributing to deepening the understanding of eutectic and deep eutectic mixtures concerning their definition, thermodynamic nature and modelling. The glut of literature on DES applications should be followed by a similar effort to address the fundamental questions on their nature. This hopefully would contribute to correct some widespread misconceptions, and help to establish a stringent definition of what a DES is. DES are eutectic mixtures for which the eutectic point temperature should be lower to that of an ideal liquid mixture. To identify and characterize them, their phase diagrams should be known, in order to compare the real temperature depression to that predicted if ideality is assumed, and to define composition ranges for which they are in the liquid state at operating temperatures. It is also shown that hydrogen bonding between the DES components should not be used to define or characterize a DES, since this would describe many ideal mixtures. The future of deep eutectic solvents is quite promising, and we expect that this work will contribute to the efficient design and selection of the best DES for a given application, and to model properties and phase equilibria without which the process design is impractical.

[1]  G. Flynn,et al.  Solid and Liquid Heat Capacities of n-Alkyl Para-aminobenzoates Near the Melting Point , 1990, Pharmaceutical Research.

[2]  Juan Ortega,et al.  Characterization and Modeling of the Liquid Phase of Deep Eutectic Solvents Based on Fatty Acids/Alcohols and Choline Chloride , 2017 .

[3]  David L Davies,et al.  Novel solvent properties of choline chloride/urea mixtures. , 2003, Chemical communications.

[4]  Burkhard König,et al.  Low melting mixtures in organic synthesis – an alternative to ionic liquids? , 2012 .

[5]  F. Gallucci,et al.  Selective separation of furfural and hydroxymethylfurfural from an aqueous solution using a supported hydrophobic deep eutectic solvent liquid membrane. , 2017, Faraday discussions.

[6]  Hai-bin Qu,et al.  Solubility of Xylose, Mannose, Maltose Monohydrate, and Trehalose Dihydrate in Ethanol–Water Solutions , 2012 .

[7]  Maaike C. Kroon,et al.  Hydrophobic deep eutectic solvents as water-immiscible extractants , 2015 .

[8]  Juan Ortega,et al.  Indirect assessment of the fusion properties of choline chloride from solid-liquid equilibria data , 2017 .

[9]  Rui L. Reis,et al.  Enhanced performance of supercritical fluid foaming of natural-based polymers by deep eutectic solvents , 2014 .

[10]  E. Tereshatov,et al.  First evidence of metal transfer into hydrophobic deep eutectic and low-transition-temperature mixtures: indium extraction from hydrochloric and oxalic acids , 2016 .

[11]  K. Row,et al.  Recent developments in deep eutectic solvents in chemical sciences , 2013, Monatshefte für Chemie - Chemical Monthly.

[12]  Richard P Matthews,et al.  Doubly ionic hydrogen bond interactions within the choline chloride-urea deep eutectic solvent. , 2016, Physical chemistry chemical physics : PCCP.

[13]  S. Yalkowsky,et al.  Estimation of the ideal solubility (crystal-liquid fugacity ratio) of organic compounds. , 2010, Journal of pharmaceutical sciences.

[14]  J. Knuutinen,et al.  Melting behaviour of D-sucrose, D-glucose and D-fructose. , 2004, Carbohydrate research.

[15]  Elena Palomo Del Barrio,et al.  New sugar alcohols mixtures for long-term thermal energy storage applications at temperatures between 70 °C and 100 °C , 2016 .

[16]  Á. Domínguez,et al.  Physicochemical Characterization of New Sulfonate and Sulfate Ammonium Ionic Liquids , 2012 .

[17]  Lifang Chen,et al.  Association extraction for vitamin E recovery from deodorizer distillate by in situ formation of deep eutectic solvent , 2017 .

[18]  J. Andanson,et al.  Impact of water on the melting temperature of urea + choline chloride deep eutectic solvent , 2016 .

[19]  E. Touitou,et al.  Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids. , 1997, Journal of pharmaceutical sciences.

[20]  M. Temprado,et al.  Vaporization, fusion and sublimation enthalpies of the dicarboxylic acids from C4 to C14 and C16 , 2005 .

[21]  Rui L. Reis,et al.  Natural Deep Eutectic Solvents – Solvents for the 21st Century , 2014 .

[22]  M. Hashim,et al.  Glycerol-based deep eutectic solvents: Physical properties , 2013 .

[23]  A. Abbott,et al.  Liquid pharmaceuticals formulation by eutectic formation , 2017 .

[24]  T. Ackermann Regular and Related Solutions , 1973 .

[25]  D. Kralisch,et al.  Conversion of carbohydrates into 5-hydroxymethylfurfural in highly concentrated low melting mixtures , 2009 .

[26]  Urvi Gala,et al.  Pharmaceutical Applications of Eutectic Mixtures , 2013 .

[27]  Gabriele Sadowski,et al.  Perturbed-Chain SAFT: An Equation of State Based on a Perturbation Theory for Chain Molecules , 2001 .

[28]  A. Soto,et al.  Properties modification by eutectic formation in mixtures of ionic liquids , 2015 .

[29]  Pablo Domínguez de María,et al.  Novel choline-chloride-based deep-eutectic-solvents with renewable hydrogen bond donors: levulinic acid and sugar-based polyols , 2012 .

[30]  I. Arends,et al.  Are Natural Deep Eutectic Solvents the Missing Link in Understanding Cellular Metabolism and Physiology?[W] , 2011, Plant Physiology.

[31]  Bärbel Kolbe,et al.  Chemical Thermodynamics for Process Simulation , 2012 .

[32]  T. Phaechamud,et al.  Transformation of eutectic emulsion to nanosuspension fabricating with solvent evaporation and ultrasonication technique , 2016, International journal of nanomedicine.

[33]  Patricia A. Hunt,et al.  Mixtures of ionic liquids. , 2012, Chemical Society reviews.

[34]  F. Ahmadi,et al.  Meloxicam transdermal delivery: effect of eutectic point on the rate and extent of skin permeation , 2014, Iranian journal of basic medical sciences.

[35]  M. Gohel,et al.  Resolving Issues of Content Uniformity and Low Permeability Using Eutectic Blend of Camphor and Menthol , 2009, Indian journal of pharmaceutical sciences.

[36]  M. C. Kroon,et al.  Low-transition-temperature mixtures (LTTMs): a new generation of designer solvents. , 2013, Angewandte Chemie.

[37]  E. A. Brignole,et al.  Phase equilibria in sugar solutions using the A-UNIFAC model , 2003 .

[38]  Geert-Jan Witkamp,et al.  Natural deep eutectic solvents as new potential media for green technology. , 2013, Analytica chimica acta.

[39]  B. Perissutti,et al.  Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals , 2016, Molecules.

[40]  Z. Tan,et al.  Heat Capacities and Nonisothermal Thermal Decomposition Reaction Kinetics of D-Mannitol , 2010 .

[41]  Catarina Florindo,et al.  Development of hydrophobic deep eutectic solvents for extraction of pesticides from aqueous environments , 2017 .

[42]  P. Kumar,et al.  Thermal and physical properties of (Choline chloride + urea + l-arginine) deep eutectic solvents , 2016 .

[43]  Enthalpy of sublimation in the study of the solid state of organic compounds. Application to erythritol and threitol. , 2005, The journal of physical chemistry. B.

[44]  Y. Marcus Unconventional Deep Eutectic Solvents: Aqueous Salt Hydrates , 2017 .

[45]  J. Gmehling,et al.  Measurement of heat capacities of ionic liquids by differential scanning calorimetry , 2006 .

[46]  M. Khan,et al.  Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: mechanism and progress of emulsion formation. , 2002, International journal of pharmaceutics.

[47]  Leonard I. Stiel,et al.  Regular and Related Solutions, Joel H. Hildebrand, John M. Prausnitz, and Rob–ert L. Scott, Van Nostrand Reinhold Co., New York (1 970). 228 pages. $10.95. , 1971 .

[48]  E. Voutsas,et al.  Estimation of the Differential Molar Heat Capacities of Organic Compounds at Their Melting Point , 2005 .

[49]  Y. Choi,et al.  Tailoring properties of natural deep eutectic solvents with water to facilitate their applications. , 2015, Food chemistry.

[50]  R. Reis,et al.  A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies , 2017, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[51]  M. Gutiérrez,et al.  Deep-eutectic solvents playing multiple roles in the synthesis of polymers and related materials. , 2012, Chemical Society reviews.

[52]  Y. Oh,et al.  Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[53]  U. S. Rai,et al.  Some Physicochemical Studies on Organic Eutectics and Molecular Complex: Urea – p-nitrophenol System , 1999 .

[54]  J. Esperança,et al.  Generating Ionic Liquids from Ionic Solids: An Investigation of the Melting Behavior of Binary Mixtures of Ionic Liquids , 2014 .

[55]  João A. P. Coutinho,et al.  Evaluation of activity coefficient models in prediction of alkane solid-liquid equilibria , 1995 .

[56]  U. Domańska,et al.  Separation of 2-phenylethanol (PEA) from water using ionic liquids , 2016 .

[57]  María de los Ángeles Fernández,et al.  Natural designer solvents for greening analytical chemistry , 2016 .

[58]  Rui L Reis,et al.  Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technology. , 2015, International journal of pharmaceutics.

[59]  I. Tetko,et al.  Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds , 2015, Molecules.

[60]  B. W. Barry,et al.  Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[61]  F. Mjalli,et al.  Fruit sugar-based deep eutectic solvents and their physical properties , 2012 .

[62]  Emma Lloyd Raven,et al.  Extraction of glycerol from biodiesel into a eutectic based ionic liquid , 2007 .

[63]  F. Guthrie LII. On eutexia , 1884 .

[64]  Lourdes F. Vega,et al.  Accurate description of thermophysical properties of Tetraalkylammonium Chloride Deep Eutectic Solvents with the soft-SAFT equation of state , 2017 .

[65]  François Jérôme,et al.  Deep eutectic solvents: syntheses, properties and applications. , 2012, Chemical Society reviews.

[66]  J. F. Liebman,et al.  ESTIMATING ENTROPIES AND ENTHALPIES OF FUSION OF ORGANIC COMPOUNDS , 1991 .

[67]  J. Mccall,et al.  Physicochemical studies of lidocaine-menthol binary systems for enhanced membrane transport. , 2000, International journal of pharmaceutics.

[68]  H. Cui,et al.  The effects of combined menthol and borneol on fluconazole permeation through the cornea ex vivo. , 2012, European journal of pharmacology.

[69]  Fan-zhu Li,et al.  Delivery of 125I-cobrotoxin after intranasal administration to the brain: a microdialysis study in freely moving rats. , 2007, International journal of pharmaceutics.

[70]  Changquan Calvin Sun,et al.  Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehicles. , 2009, International journal of pharmaceutics.

[71]  J. Coutinho,et al.  Inelastic neutron scattering study of reline: shedding light on the hydrogen bonding network of deep eutectic solvents. , 2017, Physical chemistry chemical physics : PCCP.

[72]  Chong-K. Kim,et al.  Improved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with Menthol , 2003, Drug delivery.

[73]  M. Coelho,et al.  Menthol-based Eutectic Mixtures: Hydrophobic Low Viscosity Solvents , 2015 .

[74]  T. Welton,et al.  A closer look into deep eutectic solvents: exploring intermolecular interactions using solvatochromic probes. , 2017, Physical chemistry chemical physics : PCCP.

[75]  Raymond K. Rasheed,et al.  Deep eutectic solvents formed between choline chloride and carboxylic acids: versatile alternatives to ionic liquids. , 2004, Journal of the American Chemical Society.

[76]  Emma L. Smith,et al.  Deep eutectic solvents (DESs) and their applications. , 2014, Chemical reviews.

[77]  E. Jong,et al.  Experimental and Modeling Studies on the Solubility of D-Arabinose, D-Fructose, D-Glucose, D-Mannose, Sucrose and D-Xylose in Methanol and Methanol-Water Mixtures , 2014 .

[78]  Vesna Najdanovic-Visak,et al.  Biocompatible choline based ionic salts:solubility in short-chain alcohols , 2013 .

[79]  Miriam Dupas Hubinger,et al.  Measurement and PC-SAFT modeling of solid-liquid equilibrium of deep eutectic solvents of quaternary ammonium chlorides and carboxylic acids , 2017 .

[80]  Rui L Reis,et al.  Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[81]  S. Barreiros,et al.  Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts. , 2017, Molecular pharmaceutics.

[82]  Mohammed Taghi Zafarani-Moattar,et al.  Phase Equilibrium of Aqueous Glycine + Choline Chloride Ionic Liquid Solutions , 2016, Journal of Solution Chemistry.

[83]  Qi Shen,et al.  Enhanced Intestinal Absorption of Daidzein by Borneol/Menthol Eutectic Mixture and Microemulsion , 2011, AAPS PharmSciTech.

[84]  C. Schick,et al.  Heat capacity and transition behavior of sucrose by standard, fast scanning and temperature-modulated calorimetry , 2014 .