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Received October 14, 2025
Revised November 10, 2025
Accepted November 20, 2025
Available online January 26, 2026
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Thermodynamic Properties and Solvation of Uracil in Water + (Methanol, or Ethanol) Mixtures at Various Temperatures
Northern Border University 1Imam Abdulrahman Bin Faisal University
Korean Chemical Engineering Research, February 2026, 64(1), 105145
https://doi.org/10.9713/kcer.2026.64.1.105145
https://doi.org/10.9713/kcer.2026.64.1.105145
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Abstract
The dissolution thermodynamics and preferential solvation of uracil (Ura) in aqueous mixtures of methanol and ethanol were systematically investigated over the temperature range 293.15–318.15 K. Experimental solubility data from the literature were analyzed using van’t Hoff and Gibbs equations to evaluate the standard thermodynamic parameters of dissolution (ΔsolH°, ΔsolS°, ΔsolG°). The results revealed that uracil dissolution was an endothermic and predominantly enthalpy-driven process across all solvent compositions, with solubility noticeably enhanced in intermediate alcohol-rich regions (x1 0.35–0.45). The inverse Kirkwood–Buff integrals (IKBI) approach was employed to determine the preferential solvation parameter (δx1,Ura), providing molecular-level insight into solute – solvent interactions. Positive δx1,Ura values in water-rich mixtures indicated preferential hydration, while negative values in alcohol-rich systems reflected the progressive replacement of water by alcohol in the cybotactic region around Ura. Temperature elevation reduced the magnitude of δx1,Ura, suggesting a weakening of solvent structural heterogeneity and hydrogen-bond networks. Overall, this combined thermodynamic and molecular interpretation enhanced understanding of nucleobase solvation in mixed solvents and provided a quantitative framework for optimizing pharmaceutical formulation design and solubility prediction.
References
1. Zav'yalov, S. I., Ezhova, G. I., Kravchenko, N. E., Kulikova, L. B., Dorofeeva, O. V., Rumyantseva, E. E. and Zavozin, A. G., “Natural Uracils: Synthesis and Chemical Properties (A Review),” Pharm. Chem. J., 37(7), 337-341(2003).
2. Jain, K., Sharma, S. and Utreja, D., “Uracil: A Pharmacophore with Diverse Biological Potential,” Chemistry Select., 9(5), e202303179 (2024).
3. Pałasz, A. and Cież, D., “In Search of Uracil Derivatives as Bio- active Agents. Uracils and Fused Uracils: Synthesis, Biological Activity and Applications,” Eur. J. Med. Chem., 97, 582-611(2015).
4. Pei, H., Ye, J., Wang, F., Liu, D., Yu, Y., Zhang, J. and Zhang, L., “Design, Synthesis and Herbicidal Activity of Novel Uracil Compounds Containing Piperidine Moiety,” Chin. J. Org. Chem.,(2024).
5. Nam, K., Ha, E.-S., Kim, J.-S., Kuk, D.-H., Ha, D.-H., Kim, M.- S., Cho, C.-W. and Hwang, S.-J., “Solubility of Oxcarbazepine in Eight Solvents Within the Temperature Range T=(288.15– 308.15) K,” J. Chem. Thermodyn., 104, 45-49(2017).
6. Jouyban, A., Handbook of solubility data for pharmaceuticals. Boca Raton: CRC Press; 2010.
7. Marcus, Y., Solvent Mixtures: Properties and Selective Solva- tion: Marcel Dekker, New York; 2002.
8. Marcus, Y., Preferential solvation in mixed solvents, in: P.E. Smith, E. Matteoli J.P. O’Connell (Eds.), Fluctuation Theory of Solutions: Applications in Chemistry, Chemical Engineering, and Biophysics, CRC, Press Taylor & Francis Group, BocaRaton, FL; 2013.
9. Marcus, Y., “On the Preferential Solvation of Drugs and PAHs in Binary Solvent Mixtures,” Journal of Molecular Liquids., 140(1-3), 61-67(2008).
10. Delgado, D. R., Holguín, A. R., Almanza, O. A., Martínez, F. and Marcus, Y., “Solubility and Preferential Solvation of Meloxi- cam in Ethanol+water Mixtures,” Fluid Phase Equilib., 305(1), 88-95(2011).
11. Jouyban, A., Acree, W. E. and Martínez, F., “Modeling the Sol- ubility and Preferential Solvation of Gallic Acid in Cosolvent Plus Water Mixtures,” J. Mol. Liq., 224, 502-506(2016).
12. Li, X., Liu, Y., Cao, Y., Cong, Y., Farajtabar, A. and Zhao, H., “Solubility Modeling, Solvent Effect, and Preferential Solvation of Thiamphenicol in Cosolvent Mixtures of Methanol, Ethanol, N,N-Dimethylformamide, and 1,4-Dioxane with Water,” J. Chem. Eng. Data., 63(6), 2219-2227(2018).
13. Tooski, H. F., Jabbari, M. and Farajtabar, A., “Solubility and Prefer- ential Solvation of the Flavonoid Naringenin in Some Aqueous/ Organic Solvent Mixtures,” J. Sol. Chem., 45(12), 1701-1714(2016).
14. Li, X., Wang, M., Du, C., Cong, Y. and Zhao, H., “Preferential Solvation of Rosmarinic Acid in Binary Solvent Mixtures of Ethanol+water and Methanol+water According to the Inverse Kirkwood–buff Integrals Method,” J. Mol. Liq., 240, 56-64(2017).
15. Zhou, Y., Han, D., Tao, T., Zhang, S., Wang, J., Gong, J. and Wang, Y., “Solubility Measurement, Thermodynamic Correlation and Molecular Simulations of Uracil in (alcohol + water) Binary Sol- vents at (283.15–318.15) K,” J. Mol. Liq., 318, 114259 (2020).
16. Zhang, F., Tang, Y., Wang, L., Xu, L. and Liu, G., “Solubility Measurement and Correlation for 2-Naphthaldehyde in Pure Organic Solvents and Methanol + Ethanol Mixtures,” J. Chem. Eng. Data., 60(8), 2502-2509(2015).
17. Wei, D., Li, H., Li, Y.-N. and Zhu, J., “Effect of Temperature on the Solubility of 3-aminopyridine in Binary Ethanol+toluene Solvent Mixtures,” Fluid Phase Equilib., 316, 132-134(2012).
18. Apelblat, A. and Manzurola, E., “Solubilities of L-aspartic, DL- aspartic, DL-glutamic, p-hydroxybenzoic, o-anisic, p-anisic, and Itaconic Acids in Water from T=278 K toT=345 K,” J. Chem. Thermodyn., 29(12), 1527-1533(1997).
19. Apelblat, A. and Manzurola, E., “Solubilities of o-acetylsalicylic, 4- aminosalicylic, 3,5-dinitrosalicylic, Andp-toluic Acid, and Mag- nesium-DL-aspartate in Water from T=(278 to 348) K,” Chem. Thermodyn., 31(1), 85-91(1999).
20. Holguín, A. R., Delgado, D. R., Martínez, F. and Marcus, Y., “Solution Thermodynamics and Preferential Solvation of Meloxi-cam in Propylene Glycol + Water Mixtures,” J. Solution Chem., 40(12), 1987-1999(2011).
21. Jiménez, D. M., Cárdenas, Z. J., Delgado, D. R., Jouyban, A. and Martínez, F., “Solubility and Solution Thermodynamics of Meloxicam in 1,4-Dioxane and Water Mixtures,” Ind. Eng. Chem. Res., 53(42), 16550-16558(2014).
22. Ha, E.-S., Ha, D.-H., Kuk, D.-H., Sim, W.-Y., Baek, I.-h., Kim, J.-S., Park, H. J. and Kim, M.-S., “Solubility of Cilostazol in the Presence of Polyethylene Glycol 4000, Polyethylene Glycol 6000, Polyvinylpyrrolidone K30, and Poly(1-vinylpyrrolidone-co- vinyl acetate) At Different Temperatures,” J. Chem. Thermodyn., 113, 6-10(2017).
23. Li, X., Wang, M., Du, C., Cong, Y. and Zhao, H., “Preferential Solvation of Rosmarinic Acid in Binary Solvent Mixtures of Ethanol + water and Methanol + water According to the Inverse Kirkwood–Buff Integrals Method,” J. Mol. Liq., 240, 56-64(2017).
24. Li, X., Liu, Y., Cao, Y., Cong, Y., Farajtabar, A. and Zhao, H., “Solubility Modeling, Solvent Effect, and Preferential Solvation of Thiamphenicol in Cosolvent Mixtures of Methanol, Ethanol, N,N-dimethylformamide, and 1, 4-dioxane with Water,” J. Chem. Eng. Data., 63(6), 2219-2227(2018).
25. Chen, J., Chen, G., Cong, Y., Du, C. and Zhao, H., “Solubility Modelling and Preferential Solvation of Paclobutrazol in co-sol- Vent Mixtures of (ethanol, n-propanol and 1,4-dioxane) + water,” J. Chem. Thermodyn., 112, 249-258(2017).
26. Delgado, D. R. and Martínez, F., “Solubility and Preferential Solvation of Sulfadiazine in Methanol+water Mixtures at Sev- eral Temperatures,” Fluid Phase Equilib., 379, 128-138(2014).
27. Noubigh, A. and Abderrabba, M., “Thermodynamic Modeling of the Solubility and Preferential Solvation of the Natural Prod- uct Vanillic Acid in Some Aqueous Mixtures of Alcohols at Dif- ferent Temperatures,” J. Chem. Eng. Data., 67(9), 2675-2686 (2022).
28. Noubigh, A. and Abderrabba, M., “Preferential Solvation of Azoxystrobin in Binary Solvent Mixtures of (methyl alcohol+ethyl ethanoate) and (n-propyl alcohol+ethyl ethanoate),” Braz J. Chem. Eng., 41(9), 1317-1325 (2024).
29. Noubigh, A., Abualreish, M.J., Tahar, L.B., “Solubility and pref- erential solvation of nimodipine and azlocillin drug compounds in (ethanol+ethyl acetate) mixtures,” Braz J Chem Eng (2024).
30. Noubigh, A., Khmissi, H. and Abderrabba, M., “Measurement, Solvent Effect, and Thermodynamic Modeling of the Solubility of Benzohydrazide and 2-Hydroxybenzohydrazide in Six Pure Solvents,” J. Chem. Eng. Data., 69(9), 3148-3156(2024).
31. Li, W., Xing, R., Zhu, Y., Farajtabar, A. and Zhao, H., “Solvent Effect, Transfer Property and Preferential Solvation of Artesu- nate in Aqueous co-solvent Mixtures of Some Alcohols,” Phys. Chem. Liq., 59(3), 454-466(2021).
32. Li, X., Feng, S., Farajtabar, A., Zhang, N., Chen, G. and Zhao, H., “Solubility Modelling, Solvent Effect and Preferential Solvation of 6-chloropurine in Several Aqueous co-solvent Mixtures Between 283.15 K and 328.15 K,” J. Chem. Thermodyn., 127, 106-116
(2018).
33. Chialvo, A. A., “Preferential Solvation in Pharmaceutical Pro- cessing: Rigorous Results, Critical Observations, and the Unrav- eling of Some Significant Modeling Pitfalls,” Fluid Phase Equilib., 587, 114212(2025).
34. Cristancho, D. M., Jouyban, A. and Martínez, F., “Solubility, Solution Thermodynamics, and Preferential Solvation of Piroxi- cam in Ethyl Acetate+ethanol Mixtures,” J. Mol. Liq., 221, 72-81
(2016).
35. Marcus, Y., The Properties of Solvents John Wiley & Sons, Chichester; 1998.
36. Delgado, D. R. and Martínez, F., “Preferential Solvation of Some Structurally Related Sulfonamides in 1-propanol+water co-solvent Mixtures,” Phys. Chem. Liq., 53(3), 293-306(2015).
37. Noubigh, A. and Abderrabba, M., “Thermodynamic Modeling of the Solubility and Preferential Solvation of the Natural Prod- uct Vanillic Acid in Some Aqueous Mixtures of Alcohols at Dif- ferent Temperatures,” J. Chem. Eng. Data., 67(9), 2675-2686(2022).
38. Noubigh, A. and Abderrabba, M., “Preferential Solvation of 5,7- dihydroxyflavone (chrysin) in Aqueous co-solvent Mixtures of Methanol and Ethanol,” Physics and Chemistry of Liquids., 60(6), 931-942(2022).
39. Martínez, F., Jouyban, A. and Acree, Jr W. E., “Solubility of Phenobarbital in Aqueous Cosolvent Mixtures Revisited: IKBI Preferential Solvation Analysis,” Physics and Chemistry of Liq- uids 55(4), 432-443(2017).
40.Marcus, Y., “Solubility and Solvation in Mixed Solvent Sys- tems,” Pure. Appl. Chem., 62(11), 2069-2076(1990).
41. Taft, R. W. and Kamlet, M. J., “The Solvatochromic Comparison Method. 2. The alpha.-scale of Solvent Hydrogen-bond Donor (HBD) Acidities,” J. Am. Chem. Soc., 98(10), 2886-2894(1976).
2. Jain, K., Sharma, S. and Utreja, D., “Uracil: A Pharmacophore with Diverse Biological Potential,” Chemistry Select., 9(5), e202303179 (2024).
3. Pałasz, A. and Cież, D., “In Search of Uracil Derivatives as Bio- active Agents. Uracils and Fused Uracils: Synthesis, Biological Activity and Applications,” Eur. J. Med. Chem., 97, 582-611(2015).
4. Pei, H., Ye, J., Wang, F., Liu, D., Yu, Y., Zhang, J. and Zhang, L., “Design, Synthesis and Herbicidal Activity of Novel Uracil Compounds Containing Piperidine Moiety,” Chin. J. Org. Chem.,(2024).
5. Nam, K., Ha, E.-S., Kim, J.-S., Kuk, D.-H., Ha, D.-H., Kim, M.- S., Cho, C.-W. and Hwang, S.-J., “Solubility of Oxcarbazepine in Eight Solvents Within the Temperature Range T=(288.15– 308.15) K,” J. Chem. Thermodyn., 104, 45-49(2017).
6. Jouyban, A., Handbook of solubility data for pharmaceuticals. Boca Raton: CRC Press; 2010.
7. Marcus, Y., Solvent Mixtures: Properties and Selective Solva- tion: Marcel Dekker, New York; 2002.
8. Marcus, Y., Preferential solvation in mixed solvents, in: P.E. Smith, E. Matteoli J.P. O’Connell (Eds.), Fluctuation Theory of Solutions: Applications in Chemistry, Chemical Engineering, and Biophysics, CRC, Press Taylor & Francis Group, BocaRaton, FL; 2013.
9. Marcus, Y., “On the Preferential Solvation of Drugs and PAHs in Binary Solvent Mixtures,” Journal of Molecular Liquids., 140(1-3), 61-67(2008).
10. Delgado, D. R., Holguín, A. R., Almanza, O. A., Martínez, F. and Marcus, Y., “Solubility and Preferential Solvation of Meloxi- cam in Ethanol+water Mixtures,” Fluid Phase Equilib., 305(1), 88-95(2011).
11. Jouyban, A., Acree, W. E. and Martínez, F., “Modeling the Sol- ubility and Preferential Solvation of Gallic Acid in Cosolvent Plus Water Mixtures,” J. Mol. Liq., 224, 502-506(2016).
12. Li, X., Liu, Y., Cao, Y., Cong, Y., Farajtabar, A. and Zhao, H., “Solubility Modeling, Solvent Effect, and Preferential Solvation of Thiamphenicol in Cosolvent Mixtures of Methanol, Ethanol, N,N-Dimethylformamide, and 1,4-Dioxane with Water,” J. Chem. Eng. Data., 63(6), 2219-2227(2018).
13. Tooski, H. F., Jabbari, M. and Farajtabar, A., “Solubility and Prefer- ential Solvation of the Flavonoid Naringenin in Some Aqueous/ Organic Solvent Mixtures,” J. Sol. Chem., 45(12), 1701-1714(2016).
14. Li, X., Wang, M., Du, C., Cong, Y. and Zhao, H., “Preferential Solvation of Rosmarinic Acid in Binary Solvent Mixtures of Ethanol+water and Methanol+water According to the Inverse Kirkwood–buff Integrals Method,” J. Mol. Liq., 240, 56-64(2017).
15. Zhou, Y., Han, D., Tao, T., Zhang, S., Wang, J., Gong, J. and Wang, Y., “Solubility Measurement, Thermodynamic Correlation and Molecular Simulations of Uracil in (alcohol + water) Binary Sol- vents at (283.15–318.15) K,” J. Mol. Liq., 318, 114259 (2020).
16. Zhang, F., Tang, Y., Wang, L., Xu, L. and Liu, G., “Solubility Measurement and Correlation for 2-Naphthaldehyde in Pure Organic Solvents and Methanol + Ethanol Mixtures,” J. Chem. Eng. Data., 60(8), 2502-2509(2015).
17. Wei, D., Li, H., Li, Y.-N. and Zhu, J., “Effect of Temperature on the Solubility of 3-aminopyridine in Binary Ethanol+toluene Solvent Mixtures,” Fluid Phase Equilib., 316, 132-134(2012).
18. Apelblat, A. and Manzurola, E., “Solubilities of L-aspartic, DL- aspartic, DL-glutamic, p-hydroxybenzoic, o-anisic, p-anisic, and Itaconic Acids in Water from T=278 K toT=345 K,” J. Chem. Thermodyn., 29(12), 1527-1533(1997).
19. Apelblat, A. and Manzurola, E., “Solubilities of o-acetylsalicylic, 4- aminosalicylic, 3,5-dinitrosalicylic, Andp-toluic Acid, and Mag- nesium-DL-aspartate in Water from T=(278 to 348) K,” Chem. Thermodyn., 31(1), 85-91(1999).
20. Holguín, A. R., Delgado, D. R., Martínez, F. and Marcus, Y., “Solution Thermodynamics and Preferential Solvation of Meloxi-cam in Propylene Glycol + Water Mixtures,” J. Solution Chem., 40(12), 1987-1999(2011).
21. Jiménez, D. M., Cárdenas, Z. J., Delgado, D. R., Jouyban, A. and Martínez, F., “Solubility and Solution Thermodynamics of Meloxicam in 1,4-Dioxane and Water Mixtures,” Ind. Eng. Chem. Res., 53(42), 16550-16558(2014).
22. Ha, E.-S., Ha, D.-H., Kuk, D.-H., Sim, W.-Y., Baek, I.-h., Kim, J.-S., Park, H. J. and Kim, M.-S., “Solubility of Cilostazol in the Presence of Polyethylene Glycol 4000, Polyethylene Glycol 6000, Polyvinylpyrrolidone K30, and Poly(1-vinylpyrrolidone-co- vinyl acetate) At Different Temperatures,” J. Chem. Thermodyn., 113, 6-10(2017).
23. Li, X., Wang, M., Du, C., Cong, Y. and Zhao, H., “Preferential Solvation of Rosmarinic Acid in Binary Solvent Mixtures of Ethanol + water and Methanol + water According to the Inverse Kirkwood–Buff Integrals Method,” J. Mol. Liq., 240, 56-64(2017).
24. Li, X., Liu, Y., Cao, Y., Cong, Y., Farajtabar, A. and Zhao, H., “Solubility Modeling, Solvent Effect, and Preferential Solvation of Thiamphenicol in Cosolvent Mixtures of Methanol, Ethanol, N,N-dimethylformamide, and 1, 4-dioxane with Water,” J. Chem. Eng. Data., 63(6), 2219-2227(2018).
25. Chen, J., Chen, G., Cong, Y., Du, C. and Zhao, H., “Solubility Modelling and Preferential Solvation of Paclobutrazol in co-sol- Vent Mixtures of (ethanol, n-propanol and 1,4-dioxane) + water,” J. Chem. Thermodyn., 112, 249-258(2017).
26. Delgado, D. R. and Martínez, F., “Solubility and Preferential Solvation of Sulfadiazine in Methanol+water Mixtures at Sev- eral Temperatures,” Fluid Phase Equilib., 379, 128-138(2014).
27. Noubigh, A. and Abderrabba, M., “Thermodynamic Modeling of the Solubility and Preferential Solvation of the Natural Prod- uct Vanillic Acid in Some Aqueous Mixtures of Alcohols at Dif- ferent Temperatures,” J. Chem. Eng. Data., 67(9), 2675-2686 (2022).
28. Noubigh, A. and Abderrabba, M., “Preferential Solvation of Azoxystrobin in Binary Solvent Mixtures of (methyl alcohol+ethyl ethanoate) and (n-propyl alcohol+ethyl ethanoate),” Braz J. Chem. Eng., 41(9), 1317-1325 (2024).
29. Noubigh, A., Abualreish, M.J., Tahar, L.B., “Solubility and pref- erential solvation of nimodipine and azlocillin drug compounds in (ethanol+ethyl acetate) mixtures,” Braz J Chem Eng (2024).
30. Noubigh, A., Khmissi, H. and Abderrabba, M., “Measurement, Solvent Effect, and Thermodynamic Modeling of the Solubility of Benzohydrazide and 2-Hydroxybenzohydrazide in Six Pure Solvents,” J. Chem. Eng. Data., 69(9), 3148-3156(2024).
31. Li, W., Xing, R., Zhu, Y., Farajtabar, A. and Zhao, H., “Solvent Effect, Transfer Property and Preferential Solvation of Artesu- nate in Aqueous co-solvent Mixtures of Some Alcohols,” Phys. Chem. Liq., 59(3), 454-466(2021).
32. Li, X., Feng, S., Farajtabar, A., Zhang, N., Chen, G. and Zhao, H., “Solubility Modelling, Solvent Effect and Preferential Solvation of 6-chloropurine in Several Aqueous co-solvent Mixtures Between 283.15 K and 328.15 K,” J. Chem. Thermodyn., 127, 106-116
(2018).
33. Chialvo, A. A., “Preferential Solvation in Pharmaceutical Pro- cessing: Rigorous Results, Critical Observations, and the Unrav- eling of Some Significant Modeling Pitfalls,” Fluid Phase Equilib., 587, 114212(2025).
34. Cristancho, D. M., Jouyban, A. and Martínez, F., “Solubility, Solution Thermodynamics, and Preferential Solvation of Piroxi- cam in Ethyl Acetate+ethanol Mixtures,” J. Mol. Liq., 221, 72-81
(2016).
35. Marcus, Y., The Properties of Solvents John Wiley & Sons, Chichester; 1998.
36. Delgado, D. R. and Martínez, F., “Preferential Solvation of Some Structurally Related Sulfonamides in 1-propanol+water co-solvent Mixtures,” Phys. Chem. Liq., 53(3), 293-306(2015).
37. Noubigh, A. and Abderrabba, M., “Thermodynamic Modeling of the Solubility and Preferential Solvation of the Natural Prod- uct Vanillic Acid in Some Aqueous Mixtures of Alcohols at Dif- ferent Temperatures,” J. Chem. Eng. Data., 67(9), 2675-2686(2022).
38. Noubigh, A. and Abderrabba, M., “Preferential Solvation of 5,7- dihydroxyflavone (chrysin) in Aqueous co-solvent Mixtures of Methanol and Ethanol,” Physics and Chemistry of Liquids., 60(6), 931-942(2022).
39. Martínez, F., Jouyban, A. and Acree, Jr W. E., “Solubility of Phenobarbital in Aqueous Cosolvent Mixtures Revisited: IKBI Preferential Solvation Analysis,” Physics and Chemistry of Liq- uids 55(4), 432-443(2017).
40.Marcus, Y., “Solubility and Solvation in Mixed Solvent Sys- tems,” Pure. Appl. Chem., 62(11), 2069-2076(1990).
41. Taft, R. W. and Kamlet, M. J., “The Solvatochromic Comparison Method. 2. The alpha.-scale of Solvent Hydrogen-bond Donor (HBD) Acidities,” J. Am. Chem. Soc., 98(10), 2886-2894(1976).
