Addressing the Reuse of Deep Eutectic Solvents in Li-ion Battery Recycling: Insights Into Dissolution Mechanism, Metal Recovery, Regeneration and Decomposition.

Deep eutectic solvents (DESs) have garnered attention in Li-ion battery (LIB) recycling due to their declared eco-friendly attributes and adjustable metal dissolution selectivity, offering a promising avenue for recycling processes. However, DESs currently lack competitiveness compared to mineral acids, commonly used in industrial-scale LIB recycling. Current research primarily focuses on optimizing DES formulation and experimental conditions to maximize metal dissolution yields in standalone leaching experiments. While achieving yields comparable to traditional leaching systems is important, extensive DES reuse is vital for overall recycling feasibility. To achieve this, evaluating the metal dissolution mechanism can assist in estimating DES consumption rates and assessing process makeup stream costs. The selection of appropriate metal recovery and DES regeneration strategies is essential to enable subsequent reuse over multiple cycles. Finally, decomposition of DES components should be avoided throughout the designed recycling process, as by-products can impact leaching efficiency and compromise the safety and environmental friendliness of DES. In this review, these aspects are emphasized with the aim of directing research efforts away from simply pursuing the maximization of metal dissolution efficiency, towards a broader view focusing on the application of DES beyond the laboratory scale.

Mesoscale Clusters in the Crystallisation of Organic Molecules.

The early stages of the molecular self-assembly pathway leading to crystal nucleation have a significant influence on the properties and purity of organic materials. This mini review collates the work on organic mesoscale clusters and discusses their importance in nucleation processes, with a particular focus on their critical properties and susceptibility to sample treatment parameters. This is accomplished by a review of detection methods, including dynamic light scattering, nanoparticle tracking analysis, small angle X-ray scattering, and transmission electron microscopy. Considering the challenges associated with crystallisation of flexible and large-molecule active pharmaceutical ingredients, the dynamic nature of mesoscale clusters has the potential to expand the discovery of novel crystal forms. By collating literature on mesoscale clusters for organic molecules, a more comprehensive understanding of their role in nucleation will evolve and can guide further research efforts.

New Solid Forms of Griseofulvin: A Solvate and a Relict Polymorph Related to Reported Solvates.

This work presents two new solid forms, a polymorph and a solvate, of the antifungal active pharmaceutical ingredient griseofulvin (GSF). The novel forms were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The new polymorphic form (GSF Form VI) was obtained upon drying at room temperature the GSF-acetonitrile solvate. GSF Form VI is a relict structure related to reported solvates of GSF. Thermal stability studies show that Form VI is metastable and monotropically related to the stable GSF Form I. The new GSF-n-butyl acetate solvate was obtained by crystallization from an n-butyl acetate solution. The stoichiometry of the n-butyl acetate solvate is 1:0.5. The solvate loses the solvent from the crystal lattice at a temperature between 363.15 and 374.15 K.

Solubility of ammonium metal fluorides in aqueous ethanol mixtures - implications for scandium recovery by antisolvent crystallization.

The recovery of scandium from waste streams of other mining and metallurgical processing industries is gaining research interest due to the scarcity of scandium-containing ores. Hydrometallurgical techniques such as leaching, solvent extraction and crystallization amongst others have been successfully applied to recover scandium salts from such waste streams. Scandium can be recovered as (NH4)3ScF6 by antisolvent crystallization from NH4F strip liquors obtained after solvent extraction. The coextraction of metal impurities such as Fe, Al, Zr and Ti causes contamination of the final solid product. The extent of coprecipitation of ammonium metal fluorides depends on their initial concentration in the strip liquor and their solubility in the NH4F-antisolvent mixtures. Here, the solubility of ammonium metal fluorides of Sc, Zr, Fe, Al and Ti is reported separately in 3 mol L-1 NH4F-ethanol mixtures at 25 °C as well as in a system containing all five solid phases. The solubility of (NH4)3ZrF7 is slightly higher than that of (NH4)3ScF6, while the solubilities of (NH4)3FeF6 and (NH4)3AlF6 are significantly lower in comparison to (NH4)3ScF6. The solubility of (NH4)2TiF6 is 1-2 orders of magnitude higher than those of other ammonium metal fluorides. When a mixture of ammonium metal fluoride salts is dissolved in the same 3 mol L-1 NH4F-ethanol mixture as for the individual salts, the resultant solubility of the ammonium metal fluorides of Sc, Zr and Fe decreases significantly, while the resultant solubility of ammonium aluminum hexafluoride increases. This is likely due to changes in solution speciation with increased NH4F concentration and ionic strength.

Impregnation of preparative high-performance solid phase extraction chromatography columns by organophosphorus acid compounds.

The flexible and reversible preparation of columns for use in high-performance solid phase extraction chromatography by physisorption of organophosphorus acid extractants has been investigated in detail. Two extractants have been evaluated, bis (2-ethyl-1-hexyl) phosphoric acid (HDEHP) and 2-ethyl-1-hexyl (2-ethyl-1-hexyl) phosphonic acid (HEHEHP), but the developed procedure should be broadly applicable to other extractants. The liquid-liquid solubility of the extractants in feed solvents consisting of aqueous ethanol solutions of varying composition has been determined. The total amount of adsorbed extractant has been quantified by complete desorption and elution with ethanol followed by acid-base titrimetry. Column impregnation with feed solutions of varying concentration in the undersaturated region has been systematically evaluated, and the influence of a subsequent water wash step has been explored. It is shown that to achieve a robust and reproducible physisorption, the adsorbed amount of extractant should be determined after the wash step, and care must be taken when using indirect methods of measurement. Equilibrium Langmuir-type adsorption isotherms as a function of the extractant concentration in the feed solution have been determined. Adsorption of HEHEHP is higher than HDEHP for equal feed compositions, but the solubility of HEHEHP is lower, resulting in approximately identical maximum coverage levels. The ability of the resulting columns to separate rare earth elements have been verified for a mixture of eight metals using a combined isocratic and gradient elution of nitric acid.

Characterization and Crystal Nucleation Kinetics of a New Metastable Polymorph of Piracetam in Alcoholic Solvents.

A new polymorph of the drug active pharmaceutical ingredient piracetam (Form VI) has been discovered and characterized by X-ray powder diffraction (PXRD), solid-state Raman, attenuated total reflectance infrared spectroscopy, and differential scanning calorimetry. The PXRD diffractogram of Form VI shows a distinct peak at 24.2° (2θ) that distinguishes it from the previously known polymorphs and solvates. Form VI is metastable with respect to the previously known polymorphs Form II and Form III; in ethanol solution at 288 K, Form VI transforms into Form II within 15 min, while in isopropanol solution Form VI is kinetically stable for at least 6 h. A total of 1200 crystal nucleation induction time experiments of piracetam in ethanol and isopropanol solutions have been conducted, in sets of 40-80 repeat experiments carried out at different temperatures and solute concentrations. Each solution nucleated as a single polymorph, and each set of repeat experiments resulted in different proportions of Form II, Form III, and Form VI, with Form VI dominating at low nucleation temperatures and Form II at higher nucleation temperatures. The induction time data for Form VI at 288 K have been evaluated within the framework of the classical nucleation theory. At equal driving force, nucleation of Form VI is less obstructed in ethanol than in isopropanol, as captured by a lower interfacial energy and higher pre-exponential factor in ethanol. The proportion of Form VI obtained at a comparable driving force increases in the order ethanol < isopropanol.

Solubility and thermodynamic analysis of famotidine polymorphs in pure solvents.

The present study investigates the solubility of famotidine polymorphs forms A and B between 298.15 K and 348.15 K in a range of pure solvents: water, methanol, ethanol, isopropanol and acetonitrile. Empirical and semi-empirical models have been fitted to solubility data determined experimentally by a gravimetric method. The solid phases have been characterized by FTIR and Raman spectroscopy, SEM and PXRD. In addition, heat capacities and melting data determined by DSC have been used to estimate the fusion thermodynamics and the activity of the solid phases as a function of temperature. The relationship between the famotidine polymorphs is monotropic, with form A being the stable polymorph. For both polymorphs, in terms of mass ratio, the solubility in the studied solvents decreases in the order methanol > water > ethanol > acetonitrile > isopropanol. The activity coefficient at saturation in all the solutions exceeds unity, showing a positive deviation with respect to ideality, which translates into solubilities significantly lower than the ideal values. Among the alcohols, a consistent correlation is observed between the polarity and the order of solubility.The Hildebrand solubility parameter is also well correlated with the order of solubilities in the studied solvents, with a higher solubility in more polar solvents, revealing the importance of the hydrogen bonding of the sulfamoyl group oxygens.

Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents.

The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 °C-30 °C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC). The isobaric solid state heat capacities have been measured by DSC. The quantitative thermodynamic stability relationship has been determined in a comprehensive thermodynamic analysis of the calorimetric data. The solubility of both polymorphs has been determined in eight pure organic solvents over the temperature range 278 K-323 K by a gravimetric method. The mole fraction solubility of benzocaine decreases in the order: 1,4-dioxane, acetone, ethyl acetate, chloroform, acetonitrile, methanol, n-butanol and toluene. Comparison with the determined activity of solid benzocaine forms shows that negative deviation from Raoult's law ideality is found in dioxane, acetone and ethyl acetate solutions, and positive deviation in solutions of the other investigated solvents.

Solubility and thermodynamic analysis of ketoprofen in organic solvents.

The solubility of the racemic solid phase of ketoprofen (KTP) in methanol, ethanol, isopropanol, butanol, acetonitrile, ethyl acetate, 1,4-dioxane and toluene has been determined between 273 and 303 K by a gravimetric method. FTIR and Raman spectroscopy, SEM and PXRD, have been used to characterise the solid phase. The melting data and heat capacity of solid and melt have been determined by DSC, and used to estimate fusion thermodynamics and the activity of the solid phase as functions of temperature. Empirical and semi-empirical models have been fitted to experimental solubility data. The solution activity coefficients reveal positive deviation from ideality in all solvents except for in dioxane, and very close to ideality in methanol. The solubility is fairly high in the alcohols but decrease with increasing hydrocarbon chain. Generally and due to the presence of the carboxylic acid group, KTP is more readily dissolved in polar protic solvents, followed in order by polar aprotic and non-polar solvents. However, the highest solubility is found in dioxane, classified as a non-polar solvent, but notably though the molecule having two strong hydrogen bond accepting functionalities, and no hydrogen bond donation capability.

Solubility of Two Polymorphs of Tolbutamide in n-Propanol: Comparison of Methods.

The solid-liquid solubility of two polymorphs of the title compound has been measured in n-propanol over the temperature range (278 K-303 K) by an isothermal, gravimetric method and a low heating rate polythermal method. Due to marked differences in the settling behavior of crystals of the two polymorphs in the investigated solvent, it is found that the low heating rate polythermal method gives the overall best performance for this particular system. Systematic slurry conversion experiments show that FII is the stable polymorph over the investigated temperature range (268 K-308 K). Solubility data for both polymorphs is well correlated, and has been extrapolated to the melting point, by a previously proposed semi-empirical regression model based on solid-phase calorimetric data. The system exhibits a marked positive deviation from Raoult's law, with solute activity coefficients at equilibrium decreasing with increasing temperature.

Solid and Solution State Thermodynamics of Polymorphs of Butamben (Butyl 4-Aminobenzoate) in Pure Organic Solvents.

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.

Solute clustering in undersaturated solutions - systematic dependence on time, temperature and concentration.

Molecular clustering and solvent-solute interactions in isopropanol solutions of fenoxycarb have been thoroughly and systematically investigated by dynamic light scattering, small-angle X-ray scattering, and nanoparticle tracking, supported by infrared spectroscopy and molecular dynamics simulations. The existence of molecular aggregates, clusters, ranging in size up to almost a micrometre is clearly recorded at undersaturated as well as supersaturated conditions by all three analysis techniques. The results systematically reveal that the cluster size increases with solute concentration and time at stagnant conditions. For most concentrations the time scale of cluster growth is of the order of days. In undersaturated solutions the size appears to eventually reach a maximum value, higher the higher the concentration. Below a certain concentration threshold clusters are significantly smaller. Clusters are found to be smaller in solutions pre-heated at a higher temperature, which offers a possible explanation for the so-called "history of solution" effect. The cluster distribution is influenced by filtration through membranes with a pore size of 0.1 µm, offering an alternative explanation for the "foreign particle-catalysed nucleation" effect. At moderate concentrations larger clusters appear to be sheared into smaller ones, but the original size distribution is rapidly re-established. At higher concentrations, although still well below solubility, the cluster size as well as solute concentration are strongly affected, suggesting that larger clusters contain at least a core of more organized molecules not able to pass through the filter.

Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents.

Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for 2 polymorphs of the drug tolbutamide: FI(H) and FV. Heat capacities have been determined by temperature-modulated DSC for 4 polymorphs: FI(L), FI(H), FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI(H) through a thermodynamic cycle. Calorimetric data have been used to derive a quantitative polymorphic stability relationship between these 4 polymorphs, showing that FII is the stable polymorph below approximately 333 K, above which temperature FI(H) is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI(L) and FI(H) has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in 5 pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile, and toluene) over the temperature range 278 to 323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the 5 solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are nonlinear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data have been correlated and extrapolated to the melting point using a semiempirical regression model.

Solubility and crystal nucleation in organic solvents of two polymorphs of curcumin.

Two crystal polymorphs of 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin) have been obtained by crystallization from ethanol (EtOH) solution. The polymorphs have been characterized by differential scanning calorimetry, infrared spectroscopy, and X-ray powder diffraction and shown to be the previously described forms I and III. The solubility of both polymorphs in EtOH and of one polymorph in ethyl acetate (EA) has been measured between 10°C and 50°C with a gravimetric method. Primary nucleation of curcumin from EtOH solution has been investigated in 520 constant temperature crystallization experiments in sealed, magnetically stirred vials under different conditions of supersaturation, temperature, and agitation rate. By a thermodynamic analysis of the melting data and solubility of form I, the solid-state activity is estimated from 10°C up to the melting point. The solubility is lower in EtOH than in EA, and in both solvents, a positive deviation from Raoult's law is observed. Form I has lower solubility than form III and is accordingly thermodynamically more stable over the investigated temperature interval. Extrapolation of solubility regression models indicates that there should be a low-temperature enantiotropic transition point, below which form I will be metastable. By slurry conversion experiments, it is established that this temperature is below -30°C. All nucleation experiments resulted in the stable form I. The induction time is observed to decrease with increasing agitation rate up to a certain point, and then increase with further increasing agitation rate; a trend previously observed for other compounds. By correlating the induction time data obtained at different supersaturation and temperature, the interfacial energy of form I in EtOH is estimated to be 3.0 mJ/m(2) .

Analysis of the structure and morphology of fenoxycarb crystals.

In this paper, we have explored the relationship between surface structure and crystal growth and morphology of fenoxycarb (FC). Experimental vs. predicted morphologies/face indices of fenoxycarb crystals are presented. Atomic-scale surface structures of the crystalline particles, derived from experimentally indexed single crystals, are also modelled. Single crystals of fenoxycarb exhibit a platelet-like morphology which closely matches predicted morphologies. The solvent choice does not significantly influence either morphology or crystal habit. The crystal morphology is dominated by the {001} faces, featuring weakly interacting aliphatic or aromatic groups at their surfaces. Two distinct modes of interaction of a FC molecule in the crystal can be observed, which appear to be principal factors governing the microscopic shape of the crystal: the relatively strong collateral and the much weaker perpendicular bonding. Both forcefield-based and quantum-chemical calculations predict that the aromatic and aliphatic terminated {001} faces have comparably high stability as a consequence of weak intermolecular bonding. Thus we predict that the most developed {001} surfaces of fenoxycarb crystals should be terminated randomly, favouring neither aliphatic nor aromatic termination.

Oiling out or molten hydrate-liquid-liquid phase separation in the system vanillin-water.

Vanillin crystals in a saturated aqueous solution disappear and a second liquid phase emerges when the temperature is raised above 51 degrees C. The phenomenon has been investigated with crystallization and equilibration experiments, using DSC, TGA, XRD and hot-stage microscopy for analysis. The new liquid solidifies on cooling, appears to melt at 51 degrees C, and has a composition corresponding to a dihydrate. However, no solid hydrate can be detected by XRD, and it is shown that the true explanation is that a liquid-liquid phase separation occurs above 51 degrees C where the vanillin-rich phase has a composition close to a dihydrate. To our knowledge, liquid-liquid phase separation has not previously been reported for the system vanillin-water, even though thousands of tonnes of vanillin are produced globally every year.