Cocrystal Formation in <scp>l</scp>-Menthol/Phenol Eutectic System: Experimental Study and Thermodynamic Modeling

Alhadid, Ahmad; Jandl, Christian; Mokrushina, Liudmila; Minceva, Mirjana

doi:10.1021/acs.cgd.2c00362

Cited by 17 publications

(14 citation statements)

References 55 publications

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“…The crystallization characteristics of the DESs were determined by cryogenic XRD testing on the three DESs. All DES crystal patterns showed a significant difference from their pure materials, confirming the formation of new crystalline phases (Figure G–I). − Otherwise, the DES crystal patterns should be composed of a superposition of two pure materials’ diffraction peaks . This also showed that TBAC formed cocrystals with the three dihydric alcohols in a low-temperature state.…”

Section: Resultsmentioning

confidence: 73%

“…However, the melting point change was not enough to prove that DES solidification formed cocrystals. The COSMO-RS approach that considered the most important modes of the molecular interactions could provide accurate and efficient screening of the conformers for co-crystallization. , Among these, the excess enthalpy (Δ H ex ) of a virtual supercooled liquid for the two-component mixture relative to the pure components could be regarded as the parameter to evaluate the tendency of those two compounds to form a cocrystal, where the more negative the Δ H ex value is, the more likely it is for the compounds to form cocrystals. Table summarizes the Δ H ex values for several common HBDs and the three dihydric alcohols.…”

Section: Resultsmentioning

confidence: 99%

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Designing Deep Eutectic Solvents with Crystalline Features: A New-Generation Green Crystallization-Induced Porogen

Liu

Huang

et al. 2023

ACS Sustainable Chem. Eng.

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Freeze-casting offers a simple method to prepare super-macroporous materials. However, research on inexpensive, low-toxic, and devisable deep eutectic solvents (DESs) as potential crystallization-induced porogens remains a great challenge. In this work, we used three organics (1,6-hexanediol, 1,8-octanediol, and 1,9-nonanediol) as the hydrogen bond donors along with a hydrogen bond acceptor (tetrabutylammonium chloride, TBAC) to form the DESs. COSMOtherm was used to predict the solid–liquid phase diagram of the DESs, and the DES molar ratios [TBAC/1,6-hexanediol (1:1), TBAC/1,8-octanediol (1:2.125), and TBAC/1,9-nonanediol (1.5:1)] were screened with suitable melting points (−14.77, 22.25, and 8.34 °C). The differences in melting point, viscosity, and crystal morphology of DESs caused the hydrophobic polymethylmethacrylate cryogels (contact angle > 120°) to exhibit smaller pore sizes (a reduction of 20–50%) and a higher specific surface area (an increase of 160–390 times) relative to conventional porogens. The absorption capacities of the cryogels in dichloromethane, ethyl acetate, and liquid paraffin were 39.3, 20.4, and 13.3 g g–1, respectively. This study presented a strategy that combined COSMOtherm-assisted screening and experimental validation to design DESs with a suitable melting point and cocrystal behavior. Green and devisable DESs provided more potential for achieving an adjustable pore structure of hydrophobic cryogels.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Designing Deep Eutectic Solvents with Crystalline Features: A New-Generation Green Crystallization-Induced Porogen

Liu

Huang

et al. 2023

ACS Sustainable Chem. Eng.

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“…Second, three L-menthol-based eutectic systems containing alcohols, i.e., L-menthol/neopentyl alcohol, L-menthol/thymol, and L-menthol/phenol, are compared. L-menthol/thymol and L-menthol/phenol show strong negative deviations from the ideal behavior [ 53 , 54 ]. In contrast, L-menthol/neopentyl alcohol is an ideal eutectic system.…”

Section: Resultsmentioning

confidence: 99%

Design of Deep Eutectic Systems: Plastic Crystalline Materials as Constituents

et al. 2022

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Deep eutectic solvents (DESs) are a class of green and tunable solvents that can be formed by mixing constituents having very low melting entropies and enthalpies. As types of materials that meet these requirements, plastic crystalline materials (PCs) with highly symmetrical and disordered crystal structures can be envisaged as promising DES constituents. In this work, three PCs, namely, neopentyl alcohol, pivalic acid, and neopentyl glycol, were studied as DES constituents. The solid–plastic transitions and melting properties of the pure PCs were studied using differential scanning calorimetry. The solid–liquid equilibrium phase diagrams of four eutectic systems containing the three PCs, i.e., L-menthol/neopentyl alcohol, L-menthol/pivalic acid, L-menthol/neopentyl glycol, and choline chloride/neopentyl glycol, were measured. Despite showing near-ideal behavior, the four studied eutectic systems exhibited depressions at the eutectic points, relative to the melting temperatures of the pure constituents, that were similar to or even larger than those of strongly nonideal eutectic systems. These findings highlight that a DES can be formed when PCs are used as constituents, even if the eutectic system is ideal.

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“…The melting enthalpy of a cocrystal represents the difference between the enthalpy of the cocrystal in the solid phase and the enthalpy of the liquid solution. In previous works, ,,,, we used the volume of the cocrystal unit cellestimated from powder X-ray diffraction (PXRD) measurementsand the volume of a pure constituent unit cell to confirm the stoichiometry of the cocrystal. Thus, the cocrystal represents a solid consisting of units of each constituent in the corresponding cocrystal stoichiometric ratio.…”

Section: Methodsmentioning

confidence: 99%

“…The activity coefficients of components in the liquid solution can be calculated using various thermodynamic models. Correlative activity coefficient models could accurately describe the nonideality of various eutectic systems with cocrystal formation. , In this work, we used the nonrandom two-liquid (NRTL) equation to calculate the activity coefficients of components as follows …”

Section: Methodsmentioning

confidence: 99%

Thermodynamic Approach for Estimating the Melting Enthalpy of Cocrystals

Alhadid,

Kefalianakis,

Wendler

et al. 2024

Crystal Growth & Design

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The synthesis of cocrystals is an established and efficient method for tuning the solubility of pharmaceutical and industrially relevant compounds. Predicting the cocrystal solubility prerequisites knowledge about the melting properties and the stoichiometry of the cocrystal along with the activity coefficients of individual constituents in the liquid solution. Reliable thermodynamic models can estimate the activity coefficients of components in the liquid phase; on the other hand, predicting the cocrystal melting properties and stoichiometry remains a key challenge. In this work, we propose an approach for estimating the melting enthalpy of cocrystals, where the melting enthalpy of the cocrystal is calculated using the melting properties of its pure constituents, the cocrystal stoichiometry and melting temperature, and the enthalpy of mixing the constituents in the liquid solution. For selected model systems, we show that by using our approach, the calculated melting enthalpy allowed for predicting the cocrystal liquidus line equally well and, in some cases, better than when using the experimental melting enthalpy values. Furthermore, we apply our approach to accurately predict the complete phase diagram of binary eutectic systems with cocrystal formation, in which the properties of the cocrystals have not been reported before. The advantage of our approach is the ability to model the solid–liquid phase diagram of eutectic systems with cocrystal formation without requiring extensive investigations of the cocrystal stoichiometry and melting properties. Therefore, the approach has the capacity to fill gaps of experimental uncertainties in determining the cocrystal melting enthalpy when isolating the cocrystal is challenging. By streamlining the prediction of cocrystal melting enthalpy, our proposed approach could accelerate the identification and design of pharmaceutically active cocrystals, offering a potent tool for expediting drug development processes.

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Cocrystal Formation in l-Menthol/Phenol Eutectic System: Experimental Study and Thermodynamic Modeling

Cited by 17 publications

References 55 publications

Designing Deep Eutectic Solvents with Crystalline Features: A New-Generation Green Crystallization-Induced Porogen

Designing Deep Eutectic Solvents with Crystalline Features: A New-Generation Green Crystallization-Induced Porogen

Design of Deep Eutectic Systems: Plastic Crystalline Materials as Constituents

Thermodynamic Approach for Estimating the Melting Enthalpy of Cocrystals

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