title: Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection.
abstract: Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Cox
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Phifer
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.|Departamento de Engenharia Química, Universidade Federal de São João del-Rei, CEP: 36420-000, Ouro Branco, MG, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Ferreira da Silva
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.|Departamento de Engenharia Química, Universidade Federal de São João del-Rei, CEP: 36420-000, Ouro Branco, MG, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gonçalves Nogueira
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Ley
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: O'Loughlin
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.|Instituto de Ciência e Tecnologia, Universidade Federal dos Vales do Jequitinhonha e Mucuri, CEP: 39100-000, Diamantina, MG, Brazil.
authors.forename: Ana Karolyne
authors.initials: AK
authors.lastname: Pereira Barbosa
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Rygelski
authors.affiliation: Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, 45056, USA. PaluchAS@MiamiOH.edu.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Paluch
mesh_terms: D003198:Computer Simulation; D015394:Molecular Structure; D010226:Parabens / Q000737:chemistry*; D011789:Quantum Theory; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D010226:Parabens; D012996:Solutions; D012997:Solvents
keywords: Activity coefficient; Chemical potential; Electronic structure; Free energy of solvation; Molecular simulation; Solubility