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Related Concept Videos

Solubility03:00

Solubility

Solution, Solubility, and Solubility Equilibrium
A solution is a homogeneous mixture composed of a solvent, the major component, and a solute, the minor component. The physical state of a solution—solid, liquid, or gas—is typically the same as that of the solvent. Solute concentrations are often described with qualitative terms such as dilute (of relatively low concentration) and concentrated (of relatively high concentration).
In a solution, the solute particles (molecules, atoms, and/or ions)...
Solubility Equilibria: Overview01:09

Solubility Equilibria: Overview

When a substance such as sodium chloride is added to water, it dissolves, forming an aqueous solution. The extent of dissolution is called solubility. The process of dissolution can exist in equilibrium, just like other chemical processes. Solubility equilibria are also called precipitation equilibria because the process of solubility can be reversible. The reverse of the solubility process is called precipitation.
Solubility is important in biological and environmental processes. A notable...
Factors Affecting Solubility04:01

Factors Affecting Solubility

Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
Entropy and Solvation02:05

Entropy and Solvation

The process of surrounding a solute with solvent is called solvation. It involves evenly distributing the solute within the solvent. The rule of thumb for determining a solvent for a given compound is that like dissolves like. A good solvent has molecular characteristics similar to those of the compound to be dissolved. For example, polar solutions dissolve polar solutes, and apolar solvents dissolve apolar solutes. A polar solvent is a solvent that has a high dielectric constant (ϵ ≥ 15); an...
Physical Properties Affecting Solubility02:19

Physical Properties Affecting Solubility

Solutions of Gases in Liquids
As for any solution, the solubility of a gas in a liquid is affected by the attractive intermolecular forces between solute and solvent species. Unlike solid and liquid solutes, however, there is no solute-solute intermolecular attraction to overcome when a gaseous solute dissolves in a liquid solvent since the atoms or molecules comprising a gas are far separated and experience negligible interactions. Consequently, solute-solvent interactions are the sole...
Liquid–Solid Solutions01:29

Liquid–Solid Solutions

The process of a solid dissolving in a liquid to form a solution is governed by the solubility limit, which is the maximum amount of the solid substance, or solute, that can be dissolved in a specific volume of the liquid or solvent. As the solute dissolves, it reaches a point where no more solute can be dissolved at a given temperature - this is known as the saturation point. However, if further solute is added and it manages to dissolve, the solution becomes supersaturated. Supersaturated...

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Updated: May 19, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

Optimizing solubility: kinetic versus thermodynamic solubility temptations and risks.

Christoph Saal1, Anna Christine Petereit

  • 1Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany. christoph.saal@merckgroup.com

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|August 14, 2012
PubMed
Summary
This summary is machine-generated.

Medicinal chemists can optimize drug solubility by using thermodynamic solubility data, which accurately reflects crystalline forms. Kinetic solubility assays often yield higher, amorphous-related results, making them less reliable for lead optimization.

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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
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Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Published on: September 20, 2017

Area of Science:

  • Drug discovery and development
  • Medicinal chemistry
  • Physical chemistry

Background:

  • Lead optimization is a critical stage in drug discovery.
  • Accurate solubility assessment is essential for successful lead optimization.
  • Kinetic and thermodynamic solubility assays provide different perspectives on compound solubility.

Purpose of the Study:

  • To evaluate the utility of kinetic and thermodynamic solubility data in guiding medicinal chemistry.
  • To compare the results from kinetic and thermodynamic solubility assays for research compounds.
  • To determine which solubility measurement is more beneficial for lead optimization.

Main Methods:

  • Measured the solubility of 465 research compounds using both kinetic and thermodynamic assays.
  • Employed polarized-light microscopy in the thermodynamic assay to distinguish between crystalline and amorphous forms.
  • Compared the data obtained from both solubility measurement techniques.

Main Results:

  • Kinetic solubility measurements often reported significantly higher solubility than thermodynamic measurements.
  • Kinetic assays typically reflect the solubility of the amorphous compound.
  • Thermodynamic solubility determinations more frequently relate to the crystalline phase.

Conclusions:

  • Thermodynamic solubility data, particularly when combined with solid-state form assessment, is more valuable for optimizing research compound solubility.
  • Understanding the solid-state form is crucial for interpreting solubility data in drug discovery.
  • Thermodynamic solubility provides a more reliable basis for medicinal chemistry decisions during lead optimization.