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.

Assessment of the SM12, SM8, and SMD Solvation Models for Predicting Limiting Activity Coefficients at 298.15 K

“…At present, MOSCED parameters are available for 130 organic solvents and water [20,75]. Efforts have been made to use electronic structure calculations to predict missing MOSCED parameters, including the use of solvation free energy calculations with the SMx universal solvent models [42,[80][81][82][83][84]. While we would not expect the predicted MOSCED parameters to be as good as those regressed using experimental data, the results of the present study nonetheless would suggest they would yield acceptable results, especially for early stage process conceptualization and design applications.…”

Assessment of the SM12, SM8, and SMD Solvation Models for Predicting Limiting Activity Coefficients at 298.15 K

“…At present, MOSCED parameters are available for 130 organic solvents and water [20,74]. Efforts have been made to use electronic structure calculations to predict missing MOSCED parameters, including the use of solvation free energy calculations with the SMx universal solvent models [42,[79][80][81][82][83]. While we would not expect the predicted MOSCED parameters to be as good as those regressed using experimental data, the results of the present study nonetheless would suggest they would yield acceptable results, especially for early stage process conceptualization and design applications.…”

Prediction of Alkanolamine pKa Values by Combined Molecular Dynamics Free Energy Simulations and ab Initio Calculations

“…µ res,N V T ;∞ H+ refers to a 1M molar concentration in the ideal gas and a 1M ideal solution. to that of Coxet al 13 Starting with the gas phase cc-pVTZ optimized minimum energy While there exist numerous studies addressing the effects of the charge model for neutral species on the resulting hydration free energies, 59,60 this has been rarely studied for ionized species. A main reason is that such data for ionized species is generally inaccessible experimentally.…”