The structural pathway from its solvated molecular state to the solution crystallisation of the α- and β-polymorphic forms of para amino benzoic acid

Abstract

Para amino benzoic acid has two well-characterised polymorphic forms and, whilst both crystallise in the monoclinic space group, they have quite different crystal chemistry and crystallisability behaviour. The molecular conformation...

Influence of Solvent Selection on the Crystallizability and Polymorphic Selectivity Associated with the Formation of the “Disappeared” Form I Polymorph of Ritonavir

“…In silico methods, such as molecular dynamics (MD) simulations, have been widely used to capture the dynamical behavior of the explicit intermolecular interactions within the solution phase both qualitatively and also quantitatively by developing an understanding of the molecular and intermolecular assembly behavior during the crystal nucleation process associated with crystallization from solutions (e.g., refs ,– ). Recently, some detailed methods have been developed to characterize the propensity of incipient bulk synthons within the solution state through the targeted analysis of the MD trajectory files. ,, …”

Influence of the crystallisation solution environment on the structural pathway from solute solvation to the polymorphic forms of tolfenamic acid

“…[2][3][4] Characterisation of the structures of the solute entities at their different stages in assembly from nucleation-related clusters to crystals within the crystallisation processes can provide an effective approach to understand the influence of process conditions on polymorphic outcomes. A variety of techniques have been applied to capture both the molecular and super-molecular (synthonic) ordering within these clusters in solution prior to their crystallisation, such as Fourier transform infrared (FTIR) spectroscopy, [5][6][7] Raman spectroscopy, 8,9 Ultraviolet-visible (UV/vis) spectroscopy, 10 Nuclear Magnetic Resonance (NMR) spectroscopy [11][12][13][14][15] and X-ray scattering. 5,[16][17][18][19][20] Such knowledge can provide structural information on these clusters in terms of their constituent solvent-solute interactions, the size and shape of the solute associates and their molecular conformational distributions.…”

“…Nonetheless, through a comparison of the molecular assembly behaviour through the different stages in the overall crystallisation process, the molecular evolution pathway associated with the creation and development of the various polymorphic forms can, in principle, be elucidated. 5,7,[21][22][23] The development of computational molecular-scale modelling has contributed significantly to the understanding of the thermodynamic properties within the solution state, especially when integrated with experimental data. A variety of molecular-scale computation methods have been successfully applied to the characterisation of the solid state and solution chemistry, 2,5,16,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] such as ab initio quantum mechanics using density functional theory (DFT) and molecular dynamics (MD) and molecular mechanics (MM) simulations using parametrised empirical interatomic force fields.…”

“…5,7,[21][22][23] The development of computational molecular-scale modelling has contributed significantly to the understanding of the thermodynamic properties within the solution state, especially when integrated with experimental data. A variety of molecular-scale computation methods have been successfully applied to the characterisation of the solid state and solution chemistry, 2,5,16,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] such as ab initio quantum mechanics using density functional theory (DFT) and molecular dynamics (MD) and molecular mechanics (MM) simulations using parametrised empirical interatomic force fields. Although providing high accuracy, DFT calculations and MD simulations can make a significantly high demand on both computer power and calculation time.…”

“…A variety of techniques have been applied to capture both the molecular and super-molecular (synthonic) ordering within these clusters in solution prior to their crystallisation, such as Fourier transform infrared (FTIR) spectroscopy, 5–7 Raman spectroscopy, 8,9 Ultraviolet–visible (UV/vis) spectroscopy, 10 Nuclear Magnetic Resonance (NMR) spectroscopy 11–15 and X-ray scattering. 5,16–20 Such knowledge can provide structural information on these clusters in terms of their constituent solvent–solute interactions, the size and shape of the solute associates and their molecular conformational distributions. Whilst the crystal structures of the materials at the micro- and macro-scales can be routinely determined using single crystal X-ray diffraction, determination of the structure and development of nano-scale clusters of solute molecules within the solution state can be much more challenging.…”