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New Insights into Thermodynamics of Solutes in Neat and Complex Solvents

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Physical Chemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 23268

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Special Issue Editors

Prof. Dr. Piotr Cysewski

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Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland
Interests: theoretical chemistry; in silico modeling; solution thermodynamics; new materials screening
Special Issues, Collections and Topics in MDPI journals

Dr. Tomasz Jeliński

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Collegium Medicum in Bydgoszcz, Department of Physical Chemistry, Nicolaus Copernicus University, Toruń, Poland
Interests: solubility of pharmaceuticals; natural deep eutectic solvents; ionic liquids; binary solvents; solution thermodynamics
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Dr. Maciej Przybyłek

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Guest Editor

Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toruń, Kurpińskiego 5, 85-950 Bydgoszcz, Poland
Interests: pharmacy; physical pharmacy; physical chemistry; biomaterials; environmental chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to invite you to participate in the Special Issue “New Insights into Thermodynamics of Solutes in Neat and Complex Solvents”. Solvents play a crucial role in various fields, such as pharmaceuticals, food technology, materials engineering, and purification or separation techniques including green extraction. They are indispensable at various stages of chemical processing in different industrial branches, starting with the extraction from raw materials and up to preparation of the final product, e.g., a drug formulation. This widespread area of solvent usage makes theoretical and experimental investigations crucial in obtaining new, more efficient solvents as well as optimizing the existing solvents. An important aspect is the environmental impact of used chemicals and, in this context, new solvent forms can lead to obtaining more environmentally friendly formulations.

The use of thermodynamic modeling methods has been widely applied in solvent selection and optimization problems that is important from the perspective of technological applications and for predicting the solubility of pharmaceutically active ingredients. Both well-known classical approaches (Wilson, Buchowski–Ksiazczak, NRTL) and molecular modeling-based methods (COSMO-RS, molecular dynamics) have been successfully used, as evidenced by various papers. This Special Issue is focused on experimental and theoretical aspects related to solubility modeling and solvent selection with particular emphasis on pharmaceutical applications and green technologies.

The potential topics include but are not limited to:

Solubility, solid–liquid (SLE) and liquid–liquid (LLE) equilibria
Binary solvent mixtures as cosolvents and antisolvent
Greener organic solvents and processing
Biodegradable, nontoxic, nonflammable biosolvents that are low-cost
Solvents and their mixtures as mobile phase, solvents as extraction agents
Cosolvents in supercritical fluid extraction
Methodology of solubility determination
Thermodynamic approaches to solution characteristics
Applications of liquid mixtures in pharmaceutical, analytical sciences, and technological advancements
Crystallization (solvent evaporation, antisolvent techniques)
Solid drug dosage solubility and dissolution rate improvement techniques (e.g., pharmaceutical cocrystals and eutectics, co-amorphous systems, micronization)
Solution-processed organic semiconductors

Prof. Dr. Piotr Cysewski
Dr. Tomasz Jeliński
Dr. Maciej Przybyłek
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

solubility
pharmaceuticals
solvent selection
green solvents
thermodynamic modeling
co-solvation
extraction
crystallization

Published Papers (10 papers)

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Editorial

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4 pages, 520 KiB

Open AccessEditorial

New Insights into Thermodynamics of Solutes in Neat and Complex Solvents

by Piotr Cysewski, Tomasz Jeliński and Maciej Przybyłek

Molecules 2022, 27(18), 6131; https://doi.org/10.3390/molecules27186131 - 19 Sep 2022

Viewed by 1328

Abstract

Solubility is one of the most important physicochemical properties, both from a practical and theoretical perspective [...] Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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Research

Jump to: Editorial

16 pages, 3021 KiB

Open AccessArticle

Application of COSMO-RS-DARE as a Tool for Testing Consistency of Solubility Data: Case of Coumarin in Neat Alcohols

by Piotr Cysewski, Tomasz Jeliński and Maciej Przybyłek

Molecules 2022, 27(16), 5274; https://doi.org/10.3390/molecules27165274 - 18 Aug 2022

Cited by 9 | Viewed by 1891

Abstract

Coumarin is a naturally occurring lactone-type benzopyrone with various applications in the pharmaceutical, food, perfume, and cosmetics industries. This hydrophobic compound is poorly soluble in water but dissolves well in protic organic solvents such as alcohols. Despite the extensive use of coumarin, there are only a few reports documenting its solubility in organic solvents, and some reported data are incongruent, which was the direct impulse for this study. To resolve this problem, a theoretical congruency test was formulated using COSMO-RS-DARE for the determination of intermolecular interaction parameters, which allowed for the identification of outliers as suspicious datasets. The perfect match between back-computed values of coumarin solubility and the experimental ones confirms the reliability of the formulated theoretical approach and its adequacy for testing solubility data consistency. As the final approval, the temperature-related coumarin solubility in seven neat alcohols was determined experimentally. Four solvents (methanol, ethanol, 1-propanol, and 2-propanol) were used for reproducibility purposes, and an additional three (1-butanol, 1-pentanol, and 1-octanol) were used to extend the information on the homologous series. The consistency of this extended solubility dataset is discussed in terms of the comparison of remeasured solubility values with the ones already published and within the series of structurally similar solvents. The proposed procedure extends the range of applicability of COSMO-RS-DARE and provides a real and useful tool for consistency tests of already published solubility data, allowing for the approval/disapproval of existing data and filling gaps in datasets. Linear regressions utilizing a 2D molecular descriptor, SpMin2_Bhm, or the distance between solute and solvent in the Hansen solubility space, R_a, were formulated for the estimation of COMSO-RS-DARE integration parameters. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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15 pages, 8611 KiB

Open AccessArticle

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

by Nazrul Haq, Adel F. Alghaith, Sultan Alshehri and Faiyaz Shakeel

Molecules 2022, 27(13), 4043; https://doi.org/10.3390/molecules27134043 - 23 Jun 2022

Cited by 8 | Viewed by 1926

Abstract

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10⁻² in PEG-400 at 318.2 K, however the least one was 1.97 × 10⁻⁷ in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10⁻²) > THP (1.70 × 10⁻²) > 2-BuOH (1.38 × 10⁻²) > 1-BuOH (1.37 × 10⁻²) > IPA (1.10 × 10⁻²) > EtOH (8.37 × 10⁻³) > EA (8.31 × 10⁻³) > DMSO (7.35 × 10⁻³) > MeOH (3.26 × 10⁻³) > PG (1.88 × 10⁻³) > EG (1.31 × 10⁻³) > water (1.14 × 10⁻⁶) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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22 pages, 3905 KiB

Open AccessArticle

New Screening Protocol for Effective Green Solvents Selection of Benzamide, Salicylamide and Ethenzamide

by Maciej Przybyłek, Anna Miernicka, Mateusz Nowak and Piotr Cysewski

Molecules 2022, 27(10), 3323; https://doi.org/10.3390/molecules27103323 - 22 May 2022

Cited by 9 | Viewed by 2479

Abstract

New protocol for screening efficient and environmentally friendly solvents was proposed and experimentally verified. The guidance for solvent selection comes from computed solubility via COSMO-RS approach. Furthermore, solute-solvent affinities computed using advanced quantum chemistry level were used as a rationale for observed solvents ranking. The screening protocol pointed out that 4-formylomorpholine (4FM) is an attractive solubilizer compared to commonly used aprotic solvents such as DMSO and DMF. This was tested experimentally by measuring the solubility of the title compounds in aqueous binary mixtures in the temperature range between 298.15 K and 313.15 K. Additional measurements were also performed for aqueous binary mixtures of DMSO and DMF. It has been found that the solubility of studied aromatic amides is very high and quite similar in all three aprotic solvents. For most aqueous binary mixtures, a significant decrease in solubility with a decrease in the organic fraction is observed, indicating that all systems can be regarded as efficient solvent-anti-solvent pairs. In the case of salicylamide dissolved in aqueous-4FM binary mixtures, a strong synergistic effect has been found leading to the highest solubility for 0.6 mole fraction of 4-FM. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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8 pages, 6723 KiB

Open AccessArticle

Drug Solubility Correlation Using the Jouyban–Acree Model: Effects of Concentration Units and Error Criteria

by Elaheh Rahimpour, Sima Alvani-Alamdari, William E. Acree, Jr. and Abolghasem Jouyban

Molecules 2022, 27(6), 1998; https://doi.org/10.3390/molecules27061998 - 20 Mar 2022

Cited by 6 | Viewed by 1518

Abstract

An important factor affecting the model accuracy is the unit expression type for solute and solvent concentrations. One can report the solute and solvent concentration in various units and compare them with various error scales. In order to investigate the unit and error scale expression effects on the accuracy of the Jouyban–Acree model, in the current study, seventy-nine solubility data sets were collected randomly from the published articles and solute and solvent concentrations in the investigated systems were expressed in various units. Mass fraction, mole fraction, and volume fraction were the employed concentration units for the solvent compositions, and mole fraction, molar, and gram/liter were the investigated concentration units for the solutes. The solubility data, with various solute/solvent concentration units, were correlated using the Jouyban–Acree model, and the accuracy of each model for correlating the data was investigated by calculating different error scales and discussed. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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15 pages, 480 KiB

Open AccessArticle

Solubility of Sulfamethazine in the Binary Mixture of Acetonitrile + Methanol from 278.15 to 318.15 K: Measurement, Dissolution Thermodynamics, Preferential Solvation, and Correlation

by Claudia Patricia Ortiz, Rossember Edén Cardenas-Torres, Fleming Martínez and Daniel Ricardo Delgado

Molecules 2021, 26(24), 7588; https://doi.org/10.3390/molecules26247588 - 14 Dec 2021

Cited by 9 | Viewed by 2576

Abstract

Solubility of sulfamethazine (SMT) in acetonitrile (MeCN) + methanol (MeOH) cosolvents was determined at nine temperatures between 278.15 and 318.15 K. From the solubility data expressed in molar fraction, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van ’t Hoff equations; on the other hand, the solubility data were modeled according to the Wilson models and NRTL. The solubility of SMT is thermo-dependent and is influenced by the solubility parameter of the cosolvent mixtures. In this case, the maximum solubility was achieved in the cosolvent mixture

w_{0.40}

at 318.15 K and the minimum in pure MeOH at 278.15 K. According to the thermodynamic functions, the SMT solution process is endothermic in addition to being favored by the entropic factor, and as for the preferential solvation parameter, SMT tends to be preferentially solvated by MeOH in all cosolvent systems; however,

δ x_{3, 1} < 0.01

, so the results are not conclusive. Finally, according to mean relative deviations (MRD%), the two models could be very useful tools for calculating the solubility of SMT in cosolvent mixtures and temperatures different from those reported in this research. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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14 pages, 3128 KiB

Open AccessArticle

Modeling the Solubility of Phenolic Acids in Aqueous Media at 37 °C

by Emilia Furia, Amerigo Beneduci, Luana Malacaria, Alessia Fazio, Chiara La Torre and Pierluigi Plastina

Molecules 2021, 26(21), 6500; https://doi.org/10.3390/molecules26216500 - 28 Oct 2021

Cited by 18 | Viewed by 1990

Abstract

In this work, the solubility of vanillic, gallic, syringic, p-coumaric, ferulic and caffeic acids was determined at 37 °C under different conditions, namely pure water and two different ionic media, NaCl(aq) and NaClO₄(aq), at different ionic strengths (i.e., 0.16, 0.50, 1.0, 2.0 and 3.0 M). The solubility in water of all the acids was found to be higher than that in both of the ionic media. Moreover, the solubility of hydroxycinnamic acids was lower than that of hydroxybenzoic acids. The activity coefficients of neutral species were calculated from these data; this knowledge is necessary when modeling the dependence of equilibrium constants on the ionic strength. Results obtained in this work can be useful for further studies regarding complex formation equilibria between these ligands and bioavailable metal cations. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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19 pages, 3286 KiB

Open AccessArticle

Thermodynamic Characteristics of Phenacetin in Solid State and Saturated Solutions in Several Neat and Binary Solvents

by Maciej Przybyłek, Anna Kowalska, Natalia Tymorek, Tomasz Dziaman and Piotr Cysewski

Molecules 2021, 26(13), 4078; https://doi.org/10.3390/molecules26134078 - 3 Jul 2021

Cited by 12 | Viewed by 3282

Abstract

The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning calorimetry and spectroscopic solubility measurements. The temperature-related heat capacity values measured for both the solid and melt states were provided and used for precise determination of the values for ideal solubility, fusion thermodynamic functions, and activity coefficients in the studied solutions. Factors affecting the accuracy of these values were discussed in terms of various models of specific heat capacity difference for phenacetin in crystal and super-cooled liquid states. It was concluded that different properties have varying sensitivity in relation to the accuracy of heat capacity values. The values of temperature-related excess solubility in aqueous binary mixtures were interpreted using the Jouyban–Acree solubility equation for aqueous binary mixtures of methanol, DMSO, DMF, 1,4-dioxane, and acetonitrile. All binary solvent systems studied exhibited strong positive non-ideal deviations from an algebraic rule of mixing. Additionally, an interesting co-solvency phenomenon was observed with phenacetin solubility in aqueous mixtures with acetonitrile or 1,4-dioxane. The remaining three solvents acted as strong co-solvents. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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15 pages, 1305 KiB

Open AccessArticle

Solubility Determination, Hansen Solubility Parameters and Thermodynamic Evaluation of Thymoquinone in (Isopropanol + Water) Compositions

by Mohammed Ghazwani, M. Yasmin Begum, Prawez Alam, Mohammed H. Alqarni, Hasan S. Yusufoglu and Faiyaz Shakeel

Molecules 2021, 26(11), 3195; https://doi.org/10.3390/molecules26113195 - 26 May 2021

Cited by 2 | Viewed by 2836

Abstract

This article studies the solubility, Hansen solubility parameters (HSPs), and thermodynamic behavior of a naturally-derived bioactive thymoquinone (TQ) in different binary combinations of isopropanol (IPA) and water (H₂O). The mole fraction solubilities (x₃) of TQ in various (IPA + H₂O) compositions are measured at 298.2–318.2 K and 0.1 MPa. The HSPs of TQ, neat IPA, neat H₂O, and binary (IPA + H₂O) compositions free of TQ are also determined. The x₃ data of TQ are regressed by van’t Hoff, Apelblat, Yalkowsky–Roseman, Buchowski–Ksiazczak λh, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models. The maximum and minimum x₃ values of TQ are recorded in neat IPA (7.63 × 10⁻² at 318.2 K) and neat H₂O (8.25 × 10⁻⁵ at 298.2 K), respectively. The solubility of TQ is recorded as increasing with the rise in temperature and IPA mass fraction in all (IPA + H₂O) mixtures, including pure IPA and pure H₂O. The HSP of TQ is similar to that of pure IPA, suggesting the great potential of IPA in TQ solubilization. The maximum molecular solute-solvent interactions are found in TQ-IPA compared to TQ-H₂O. A thermodynamic study indicates an endothermic and entropy-driven dissolution of TQ in all (IPA + H₂O) mixtures, including pure IPA and pure H₂O. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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18 pages, 14230 KiB

Open AccessArticle

Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures

by Mohammed Ghazwani, Prawez Alam, Mohammed H. Alqarni, Hasan S. Yusufoglu and Faiyaz Shakeel

Molecules 2021, 26(11), 3091; https://doi.org/10.3390/molecules26113091 - 21 May 2021

Cited by 9 | Viewed by 2269

Abstract

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy–entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2–318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van’t Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsly–Roseman, Jouyban–Acree, and van’t Hoff–Jouyban–Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10⁻²) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10⁻⁶) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization. Full article

(This article belongs to the Special Issue New Insights into Thermodynamics of Solutes in Neat and Complex Solvents)

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