The effects of the hydrostatic and shear-inducing pressure on the physicochemical properties of solids are analysed. The mechanochemical reactions and mechanical activation are illustrated with various types of chemical transformations ranging from polymorph transitions to solid-state reactions. The prospects for the use of mechanochemistry for the solution of applied problems are discussed.

https://iopscience.iop.org/article/10.1070/RC2006v075n03ABEH001205/pdf

Mechanochemistry and mechanical activation of solids

Interest in molecular crystals has grown thanks to their relevance to pharmaceuticals, organic semiconductor materials, foods, and many other applications. Electronic structure methods have become an increasingly important tool for modeling molecular crystals and polymorphism. This article reviews electronic structure techniques used to model molecular crystals, including periodic density functional theory, periodic second-order Moller-Plesset perturbation theory, fragment-based electronic structure methods, and diffusion Monte Carlo. It also discusses the use of these models for predicting a variety of crystal properties that are relevant to the study of polymorphism, including lattice energies, structures, crystal structure prediction, polymorphism, phase diagrams, vibrational spectroscopies, and nuclear magnetic resonance spectroscopy. Finally, tools for analyzing crystal structures and intermolecular interactions are briefly discussed.

/pdf/modeling-polymorphic-molecular-crystals-with-electronic-19y8mf9f42.pdf

Modeling Polymorphic Molecular Crystals with Electronic Structure Theory

Van der Waals (vdW) interactions are ubiquitous in molecules and condensed matter, and play a crucial role in determining the structure, stability, and function for a wide variety of systems. The accurate prediction of these interactions from first principles is a substantial challenge because they are inherently quantum mechanical phenomena that arise from correlations between many electrons within a given molecular system. We introduce an efficient method that accurately describes the nonadditive many-body vdW energy contributions arising from interactions that cannot be modeled by an effective pairwise approach, and demonstrate that such contributions can significantly exceed the energy of thermal fluctuations—a critical accuracy threshold highly coveted during molecular simulations—in the prediction of several relevant properties. Cases studied include the binding affinity of ellipticine, a DNA-intercalating anticancer agent, the relative energetics between the A- and B-conformations of DNA, and the thermodynamic stability among competing paracetamol molecular crystal polymorphs. Our findings suggest that inclusion of the many-body vdW energy is essential for achieving chemical accuracy and therefore must be accounted for in molecular simulations.

/pdf/collective-many-body-van-der-waals-interactions-in-molecular-4hjpw497wi.pdf

Collective many-body van der Waals interactions in molecular systems

This paper discusses the trends in the experimental studies of molecular organic solids at high pressures by diffraction techniques. Crystallization of liquids, crystallization from solutions and solid-state transformations are considered. Special attention is paid to the high-pressure studies of pharmaceuticals and of biomimetics.

/pdf/high-pressure-diffraction-studies-of-molecular-organic-5cv54a9ncv.pdf

High-pressure diffraction studies of molecular organic solids. A personal view

We show that nanoconfinement is a handle to rationally produce and stabilize otherwise metastable or transient polymorphs of pharmaceuticals, as required for controllable and efficient drug delivery. The systematic investigation of crystallization under confinement unveils thermodynamic properties of metastable polymorphs not accessible otherwise and may enhance the understanding of the crystallization behavior of pharmaceuticals in general. As an example in this case, we studied acetaminophen confined to inexpensive and biocompatible nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence that either the stable polymorph form I or the metastable polymorph form III can be stabilized in high yields. Thermodynamic parameters for form III of acetaminophen are reported, and strategies to manipulate the crystalline state in pores by thermal treatments are presented.

Manipulating the Crystalline State of Pharmaceuticals by Nanoconfinement

Polymorphism of paracetamol: Relative stabilities of the monoclinic and orthorhombic phases inferred from topological pressure‐temperature and temperature‐volume phase diagrams

Franck Leveiller

Papers

Polymorphism of paracetamol: Relative stabilities of the monoclinic and orthorhombic phases inferred from topological pressure‐temperature and temperature‐volume phase diagrams