Solubilities Inferred from the Combination of Experiment and Simulation. Case Study of Quercetin in a Variety of Solvents

Chebil, Latifa; Chipot, Christophe; Archambault, Fabien; Humeau, Catherine; Engasser, Jean‐Marc; Ghoul, Mohamed; Dagognet, François

doi:10.1021/jp104569k

Cited by 28 publications

(21 citation statements)

References 35 publications

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“…The solubility of a compound can be evaluated in any solvent of interest based on the experimentally found solubility of the compound in another solvent, and the relevant free energies of solvation computed with MD. For instance, Chebil et al [504] reproduced the solubility of quercetin in chloroform, water, acetonitrile, acetone, and tert-amyl alcohol within 0.5 log unit using the equation:…”

Section: Drug Solubilitymentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.

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Section: Drug Solubilitymentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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“…Chebil et al [5] have also determined solubilities in a few nonaqueous solvents, but only at 323 K, and so we did not use these results, especially as Althans et al [1] have shown that quercetin in water decomposes at temperatures higher than 316 K..…”

Section: Tablementioning

confidence: 99%

On the solubility of quercetin

Abraham

Acree

2014

Journal of Molecular Liquids

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There is considerable disagreement over the solubility of quercetin in water. Experimental values of log Cw with Cw in mol/L range from -2.52 to -5.89, a difference of over three log units. We have applied a methodology based on linear free energy equations for water-solvent and gassolvent partitions to study solubilities. These are related to partition coefficients through Ps = Cs/Cw where Cs and Cw are solubilities of a given solute in a solvent and in water. We find that known solubilities of quercetin in methanol and ethanol at 298 K and a known water-solvent partition coefficient can be accommodated in the same model if the water solubility at 298 K, as log Cw, is taken as -3.90, that is near to the middle of the range of experimental values. Our model successfully predicts solubilities of quercetin in water-ethanol mixtures near to the ethanol rich mixtures.

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“…It is worth emphasizing that even though the solid properties are often more difficult to study with simulation models, knowledge of the relative solubility of a compound in a solvent is highly warranted in itself. Knowledge of the relative solubility—combined with calculated solvation free energies and experimental knowledge of the solubility in one reference environment—pave the way to calculating absolute solubilities in any new solvent [15].…”

Section: Introductionmentioning

confidence: 99%

Molecular simulation as a computational pharmaceutics tool to predict drug solubility, solubilization processes and partitioning

Hossain

Kabedev

Parrow

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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In this review we will discuss how computational methods, and in particular classical molecular dynamics simulations, can be used to calculate solubility of pharmaceutically relevant molecules and systems. To the extent possible, we focus on the non-technical details of these calculations, and try to show also the added value of a more thorough and detailed understanding of the solubilization process obtained by using computational simulations. Although the main focus is on classical molecular dynamics simulations, we also provide the reader with some insights into other computational techniques, such as the COSMO-method, and also discuss Flory-Huggins theory and solubility parameters. We hope that this review will serve as a valuable starting point for any pharmaceutical researcher, who has not yet fully explored the possibilities offered by computational approaches to solubility calculations.

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Solubilities Inferred from the Combination of Experiment and Simulation. Case Study of Quercetin in a Variety of Solvents

Cited by 28 publications

References 35 publications

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

On the solubility of quercetin

Molecular simulation as a computational pharmaceutics tool to predict drug solubility, solubilization processes and partitioning

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