title: Solubility challenge: can you predict solubilities of 32 molecules using a database of 100 reliable measurements?
abstract: Solubility is a key physicochemical property of molecules. Serious deficiencies exist in the consistency and reliability of solubility data in the literature. The accurate prediction of solubility would be very useful. However, systematic errors and lack of metadata associated with measurements greatly reduce the confidence in current models. To address this, we are accurately measuring intrinsic solubility values, and here we report results for a diverse set of 100 druglike molecules at 25 degrees C and an ionic strength of 0.15 M using the CheqSol approach. This is a highly reproducible potentiometric technique that ensures the thermodynamic equilibrium is reached rapidly. Results with a coefficient of variation higher than 4% were rejected. In addition, the Potentiometric Cycling for Polymorph Creation method, [PC] (2), was used to obtain multiple polymorph forms from aqueous solution. We now challenge researchers to predict the intrinsic solubility of 32 other druglike molecules that have been measured but are yet to be published.
authors.affiliation: Pfizer Institute for Pharmaceutical Materials Science & Unilever Centre for Molecular Informatics,Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom. Antonio.Llinas@astrazeneca.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Llinàs
authors.forename: Robert C
authors.initials: RC
authors.lastname: Glen
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goodman
mesh_terms: D003628:Database Management Systems; D009994:Osmolar Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations