Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones DOI Creative Commons
Ivica Đilović, Nenad Judaš, Mario Komar

et al.

Crystals, Journal Year: 2024, Volume and Issue: 15(1), P. 39 - 39

Published: Dec. 30, 2024

Three halo-substituted phenyl-quinazolinone derivatives were prepared and structurally characterized [1 = 3-(4-chlorophenyl)-6-iodo-2-methylquinazolin-4(3H)-one, 2 6-iodo-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one, 3 7-chloro-2-methyl-3-[4-(trifluoromethoxy)phenyl]quinazolin-4(3H)-one)] in order to explore the relationship between structure melting point this group of compounds. Depending on compound, molecules are interconnected by weak π∙∙∙π interactions, have I···Cl or Cl···Cl halogen bonding, primarily form C–H∙∙∙N, C–H∙∙∙O, interactions (no bonding). The presence OCF3 leads fluorine atoms that shorter than sum van der Waals radius for fluorine, suggesting these contribute overall lattice energy. sequence points cannot be fully explained intermolecular present solid state (enthalpy factor). To address this, a concept related entropy called functional rotation influence, which relates decrease fusion caused rotational freedom polyatomic groups, was introduced. Analysis previously synthesized 3-phenylquinazolinones showed compounds with highest quinazoline-substituted phenyl-nitro-substituted ones. Among halo-phenyl-substituted compounds, follows ortho < meta para. Regarding atom type, is Cl ≈ Br > F I enantiopure racemic Also, correlates bond energy (I F) only when geometry favorable.

Language: Английский

Experimental and Machine-Learning-Assisted Design of Pharmaceutically Acceptable Deep Eutectic Solvents for the Solubility Improvement of Non-Selective COX Inhibitors Ibuprofen and Ketoprofen DOI Creative Commons
Piotr Cysewski, Tomasz Jeliński, Maciej Przybyłek

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2296 - 2296

Published: May 14, 2024

Deep eutectic solvents (DESs) are commonly used in pharmaceutical applications as excellent solubilizers of active substances. This study investigated the tuning ibuprofen and ketoprofen solubility utilizing DESs containing choline chloride or betaine hydrogen bond acceptors various polyols (ethylene glycol, diethylene triethylene glycerol, 1,2-propanediol, 1,3-butanediol) donors. Experimental data were collected for all DES systems. A machine learning model was developed using COSMO-RS molecular descriptors to predict solubility. All studied exhibited a cosolvency effect, increasing drug at modest concentrations water. The accurately predicted ibuprofen, ketoprofen, related analogs (flurbiprofen, felbinac, phenylacetic acid, diphenylacetic acid). approach enables rational design prediction formulations improved applications.

Language: Английский

Citations

16
Deep Eutectic Solvents as Agents for Improving the Solubility of Edaravone: Experimental and Theoretical Considerations DOI Creative Commons
Tomasz Jeliński, Maciej Przybyłek,

Magdalena Mianowana

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1261 - 1261

Published: March 12, 2024

In this study, both practical and theoretical aspects of the solubility edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The some media, including water, can be limited, which creates need for new efficient environmentally safe solvents. EDA was measured spectrophotometrically complex intermolecular interactions within systems studied with COSMO-RS framework. Of four DES systems, three outperformed most classical organic solvent, namely dichloromethane, comprising choline chloride triethylene glycol, acting as hydrogen bond donor (HBD), a 1:2 molar proportion yielding highest EDA. Interestingly, addition specific amount water further increased solubility. Theoretical analysis revealed that pure or solutions high content, stacking is responsible self-aggregation lower On other hand, presence HBDs leads to formation clusters EDA, reducing self-aggregation. However, stoichiometric three-molecular EDA–HBD–water formed, explains why also act co-solvent. probability type complexes related affinity components, exceeds all possible complexes.

Language: Английский

Citations

6
Experimental and Theoretical Insights into the Intermolecular Interactions in Saturated Systems of Dapsone in Conventional and Deep Eutectic Solvents DOI Creative Commons
Piotr Cysewski, Tomasz Jeliński, Maciej Przybyłek

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(8), P. 1743 - 1743

Published: April 11, 2024

Solubility is not only a crucial physicochemical property for laboratory practice but also provides valuable insight into the mechanism of saturated system organization, as measure interplay between various intermolecular interactions. The importance these data cannot be overstated, particularly when dealing with active pharmaceutical ingredients (APIs), such dapsone. It commonly used anti-inflammatory and antimicrobial agent. However, its low solubility hampers efficient applications. In this project, deep eutectic solvents (DESs) were solubilizing agents dapsone an alternative to traditional solvents. DESs composed choline chloride one six polyols. Additionally, water–DES mixtures studied type ternary in systems was determined spectrophotometrically. This study analyzed interactions, systems, wide range found literature, using COSMO-RS framework. interactions quantified affinity values, which correspond Gibbs free energy pair formation molecules constituents regular chloride-based patterns solute–solute, solute–solvent, solvent–solvent that affect recognized Orange mining software (version 3.36.2). Finally, computed values provide useful descriptors machine learning purposes. impact on neat solvents, binary organic solvent mixtures, highlighted, underscoring role self-association providing insights complex phenomena. Also diversity highlighted factor determining solubility. Non-Linear Support Vector Regression (NuSVR) model, conjunction unique molecular descriptors, revealed exceptional predictive accuracy. Overall, underscores potency characteristics models unraveling thereby advancing our understanding phenomena within scientific community.

Language: Английский

Citations

6
Solubility of dapsone in deep eutectic solvents: Experimental analysis, molecular insights and machine learning predictions DOI Creative Commons
Tomasz Jeliński, Maciej Przybyłek, Rafał Różalski

et al.

Polymers in Medicine, Journal Year: 2024, Volume and Issue: 54(1), P. 15 - 25

Published: Jan. 10, 2024

Dapsone (DAP) is an anti-inflammatory and antimicrobial active pharmaceutical ingredient used to treat, e.g., AIDS-related diseases. However, low solubility a feature hampering its efficient use.

Language: Английский

Citations

5
Navigating Solid-Form Screening Using In Silico Methods Validated with Experimental Data for a Drug-like Molecule DOI
Anantha Rajmohan Muthusamy,

Diwakar Chauhan,

Arvind Kumar Jain

et al.

Crystal Growth & Design, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

Citations

0
Predicting sulfanilamide solubility in the binary mixtures using a reference solvent approach DOI Creative Commons
Piotr Cysewski, Maciej Przybyłek, Tomasz Jeliński

et al.

Polymers in Medicine, Journal Year: 2024, Volume and Issue: 54(1), P. 27 - 34

Published: Feb. 2, 2024

Solubility is a fundamental physicochemical property of active pharmaceutical ingredients. The optimization dissolution medium aims not only to increase solubility and other aspects are be included such as environmental impact, toxicity degree, availability, costs. Obtaining comprehensive characteristics chemical compounds non-trivial demanding process. Therefore, support from theoretical approaches practical importance.

Language: Английский

Citations

2
Solubility Measurement, Model Correlation, and Solvent Effect Analysis of Spectinomycin Dihydrochloride Pentahydrate in Three Binary Solvents DOI

Dechen Wang,

Yu Zhou, Chunyan Liu

et al.

Journal of Solution Chemistry, Journal Year: 2024, Volume and Issue: 53(10), P. 1419 - 1441

Published: June 3, 2024

Language: Английский

Citations

0
Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones DOI Creative Commons
Ivica Đilović, Nenad Judaš, Mario Komar

et al.

Crystals, Journal Year: 2024, Volume and Issue: 15(1), P. 39 - 39

Published: Dec. 30, 2024

Three halo-substituted phenyl-quinazolinone derivatives were prepared and structurally characterized [1 = 3-(4-chlorophenyl)-6-iodo-2-methylquinazolin-4(3H)-one, 2 6-iodo-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one, 3 7-chloro-2-methyl-3-[4-(trifluoromethoxy)phenyl]quinazolin-4(3H)-one)] in order to explore the relationship between structure melting point this group of compounds. Depending on compound, molecules are interconnected by weak π∙∙∙π interactions, have I···Cl or Cl···Cl halogen bonding, primarily form C–H∙∙∙N, C–H∙∙∙O, interactions (no bonding). The presence OCF3 leads fluorine atoms that shorter than sum van der Waals radius for fluorine, suggesting these contribute overall lattice energy. sequence points cannot be fully explained intermolecular present solid state (enthalpy factor). To address this, a concept related entropy called functional rotation influence, which relates decrease fusion caused rotational freedom polyatomic groups, was introduced. Analysis previously synthesized 3-phenylquinazolinones showed compounds with highest quinazoline-substituted phenyl-nitro-substituted ones. Among halo-phenyl-substituted compounds, follows ortho < meta para. Regarding atom type, is Cl ≈ Br > F I enantiopure racemic Also, correlates bond energy (I F) only when geometry favorable.

Language: Английский

Citations

0