title: Salting out the polar polymorph: analysis by alchemical solvent transformation.
abstract: We computationally examine how adding NaCl to an aqueous solution with α- and γ-glycine nuclei alters the structure and interfacial energy of the nuclei. The polar γ-glycine nucleus in pure aqueous solution develops a melted layer of amorphous glycine around the nucleus. When NaCl is added, a double layer is formed that stabilizes the polar glycine polymorph and eliminates the surface melted layer. In contrast, the non-polar α-glycine nucleus is largely unaffected by the addition of NaCl. To quantify the stabilizing effect of NaCl on γ-glycine nuclei, we alchemically transform the aqueous glycine solution into a brine solution of glycine. The alchemical transformation is performed both with and without a nucleus in solution and for nuclei of α-glycine and γ-glycine polymorphs. The calculations show that adding 80 mg/ml NaCl reduces the interfacial free energy of a γ-glycine nucleus by 7.7 mJ/m(2) and increases the interfacial free energy of an α-glycine nucleus by 3.1 mJ/m(2). Both results are consistent with experimental reports on nucleation rates which suggest: J(α, brine) < J(γ, brine) < J(α, water). For γ-glycine nuclei, Debye-Hückel theory qualitatively, but not quantitatively, captures the effect of salt addition. Only the alchemical solvent transformation approach can predict the results for both polar and non-polar polymorphs. The results suggest a general "salting out" strategy for obtaining polar polymorphs and also a general approach to computationally estimate the effects of solvent additives on interfacial free energies for nucleation.
authors.affiliation: Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Duff
authors.affiliation: Department of Physics, Kansas State University, Manhattan, Kansas 66506, USA.
authors.forename: Yuba Raj
authors.initials: YR
authors.lastname: Dahal
authors.affiliation: Department of Physics, Kansas State University, Manhattan, Kansas 66506, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Schmit
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, California 93106, USA.
authors.forename: Baron
authors.initials: B
authors.lastname: Peters
mesh_terms: D005998:Glycine / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D012996:Solutions; D012997:Solvents; D014867:Water; D012965:Sodium Chloride; D005998:Glycine