Influence of Solvent and Solid-State Structure on Nucleation of Parabens

Abstract

In the present work the induction time for nucleation of ethyl paraben (EP) and propyl paraben (PP) in ethanol, ethyl acetate and acetone has been measured at different levels of supersaturation. The induction time shows a wide variation among repeat experiments, indicative of the stochastic nature of nucleation. The solid-liquid interfacial energy and the size of the critical nucleus have been determined according to the classical nucleation theory. Combined with previous results for butyl paraben (BP), the nucleation behaviour is analysed with respect to differences in the solid phase of the three pure compounds, and with respect to differences in the solution. The results indicate that the difficulty of nucleation in ethanol and acetone increases in the order BP < PP < EP, but is approximately the same in ethyl acetate. For each of the three parabens the difficulty of nucleation increases in the order acetone < ethyl acetate < ethanol. The Gibbs energy of melting increases in the order BP < PP < EP, but the crystal structures are quite similar resulting in the basic crystal shape being very much the same. The solid-liquid interfacial energy is reasonably well correlated to the solvation energy, and even better correlated to the deformation energy, of the solute molecule within the first solvation shell as obtained by density functional theory calculations.

Crystal Nucleation of Tolbutamide in Solution: Relationship to Solvent, Solute Conformation, and Solution Structure

“…[2] As determined by adoption of the classical nucleation theory,t he interfaciale nergy has been found to in some cases be inversely relatedt om acroscopic properties like the solubility, [3] and the solvent boiling point. [4] The nucleation behaviourh as also been correlated to solvationa nd deformation energies [5] as well as strength of solvent-solute binding and successive desolvation. [6,7] Evidence is growingt hat the structural arrangement of clusters of solute molecules in solution affects the subsequent nucleation.…”

Phase equilibrium and mechanisms of crystallization in liquid–liquid phase separating system

“…When butyl paraben is added into an aqueous ethanol solution in a certain range of ethanol/ water ratio, the solution separates into two liquid phases [16,22], induced by the hydrocarbon tail and the hydroxyl functional groups of the butyl paraben molecule. The solubility [18,23] and nucleation [24,25] of butyl paraben were investigated, and several cooling crystallization experiments [16,26] of butyl paraben in various mixtures were reported, revealing the obvious influence of liquidliquid phase separation on the process and the solid product. However, the mechanisms involved in crystallizing from an LLPS solution are complex and not well understood.…”

Theoretical Characterization of Hydrogen Bonding Interactions between RCHO (R = H, CN, CF3, OCH3, NH2) and HOR′(R′ = H, Cl, CH3, NH2, C(O)H, C6H5)

“…Carbonyl complexes with O-H· · · O=C bonds is also important from the crystallographic point of view. [69][70][71] For instance, Nguyen et al have analyzed the experimental electron density distribution (EDD) in the cocrystals of salicylic acid with 8-hydroxyquinoline using high resolution X-ray diffraction data. 69 They compared experimental EDD with theoretical densities evaluated using Atoms in Molecules theory using high level ab initio and BHandH calculations.…”