http://pubs.acs.org/doi/pdfplus/10.1021/cr300162p

Deep Eutectic Solvents (DESs) and Their Applications

Within the framework of green chemistry, solvents occupy a strategic place. To be qualified as a green medium, these solvents have to meet different criteria such as availability, non-toxicity, biodegradability, recyclability, flammability, and low price among others. Up to now, the number of available green solvents are rather limited. Here we wish to discuss a new family of ionic fluids, so-called Deep Eutectic Solvents (DES), that are now rapidly emerging in the current literature. A DES is a fluid generally composed of two or three cheap and safe components that are capable of self-association, often through hydrogen bond interactions, to form a eutectic mixture with a melting point lower than that of each individual component. DESs are generally liquid at temperatures lower than 100 °C. These DESs exhibit similar physico-chemical properties to the traditionally used ionic liquids, while being much cheaper and environmentally friendlier. Owing to these remarkable advantages, DESs are now of growing interest in many fields of research. In this review, we report the major contributions of DESs in catalysis, organic synthesis, dissolution and extraction processes, electrochemistry and material chemistry. All works discussed in this review aim at demonstrating that DESs not only allow the design of eco-efficient processes but also open a straightforward access to new chemicals and materials.

Deep eutectic solvents: syntheses, properties and applications

Green technology actively seeks new solvents to replace common organic solvents that present inherent toxicity and have high volatility, leading to evaporation of volatile organic compounds to the atmosphere. Over the past two decades, ionic liquids (ILs) have gained enormous attention from the scientific community, and the number of reported articles in the literature has grown exponentially. Nevertheless, IL “greenness” is often challenged, mainly due to their poor biodegradability, biocompatibility, and sustainability. An alternative to ILs are deep eutectic solvents (DES). Deep eutectic solvents are defined as a mixture of two or more components, which may be solid or liquid and that at a particular composition present a high melting point depression becoming liquids at room temperature. When the compounds that constitute the DES are primary metabolites, namely, aminoacids, organic acids, sugars, or choline derivatives, the DES are so called natural deep eutectic solvents (NADES). NADES fully represen...

Natural Deep Eutectic Solvents – Solvents for the 21st Century

How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.

Crystal engineering: from molecule to crystal.

A new generation of designer solvents emerged in the last decade as promising green media for multiple applications, including separation processes: the low-transition-temperature mixtures (LTTMs). They can be prepared by mixing natural high-melting-point starting materials, which form a liquid by hydrogen-bond interactions. Among them, deep-eutectic solvents (DESs) were presented as promising alternatives to conventional ionic liquids (ILs). Some limitations of ILs are overcome by LTTMs, which are cheap and easy to prepare from natural and readily available starting materials, biodegradable, and renewable.

Low-transition-temperature mixtures (LTTMs): a new generation of designer solvents.

A theophylline monohydrate (THm) powder, with particle size and shape substantially similar to a theophylline anhydrate powder, was prepared by vapor-mediated phase conversion. The elimination of possible contributions by particle size and shape to tableting properties made it possible to unambiguously identify the role of bonding area and bonding strength on powder tableting performance. It was also shown that accurate true density is essential for correct analysis and understanding of tableting behavior of THm. Experimental evidence revealed surprisingly high plasticity of THm. This is explained by its unique ladder-like structure, where rigid molecular dimers (rungs) weakly connect to more rigid water chains (rails). The low energy barrier for moving rigid dimers down the rigid water chains enables facile propagation of dislocations in THm crystals when subjected to an external stress.

http://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.7b00124

Superior Plasticity and Tabletability of Theophylline Monohydrate

We report here the first pharmaceutical twistable hydrogen-bonded two-dimensional plastic hydrate crystal of a well-known psychoactive drug, caffeine (CAH). The availability of two pairs of plastic...

Twistable Pharmaceutical Crystal Exhibiting Exceptional Plasticity and Tabletability

Highly soluble cocrystals can be used to improve bioavailability of a poorly soluble drug, through generating supersaturation, when absorption is limited by drug dissolution. Dihydromyricetin (DMY) is a biopharmaceutics classification system (BCS) IV drug, exhibiting dissolution limited absorption. Two novel soluble cocrystals of (±)DMY with caffeine and urea were prepared, and their physicochemical properties were evaluated for suitability in formulation development. Although having a much higher solubility than (±)DMY, both cocrystals undergo rapid precipitation during dissolution and form the poorly soluble (±)DMY dihydrate in aqueous media. This negates the potential advantage offered by the high solubility of the two cocrystals in enhancing the dissolution rate and in vivo bioavailability. To solve this problem, we have systematically evaluated suitable crystallization inhibitors to maintain the supersaturation generated by cocrystal dissolution over a prolonged period of time. At 37 °C, an approxima...

Enhancing Bioavailability of Dihydromyricetin through Inhibiting Precipitation of Soluble Cocrystals by a Crystallization Inhibitor

Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization

An analysis of compiled literature nanoindentation hardness (Hc) and elastic modulus (E) values of molecular crystals revealed a wide range of mechanical properties (0.001–1.80 GPa for Hc and 0.27–46.8 GPa for E). A global approximately linear relationship between E and Hc is observed and possible reasons for deviation from the line are discussed. A classification scheme for molecular crystals based on E and Hc is proposed. In addition, results suggest that the effectiveness of crystal engineering strategies in modifying both E and Hc follows the order cocrystallization/salt formation > polymorph formation > anisotropy. A clear understanding of the E and Hc landscape lays a foundation for effective optimization of the mechanical properties of molecular crystals through crystal engineering.

Changquan Calvin Sun

Papers

Superior Plasticity and Tabletability of Theophylline Monohydrate

Twistable Pharmaceutical Crystal Exhibiting Exceptional Plasticity and Tabletability

Enhancing Bioavailability of Dihydromyricetin through Inhibiting Precipitation of Soluble Cocrystals by a Crystallization Inhibitor

Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization

The landscape of mechanical properties of molecular crystals