Control and prediction of the organic solid state: a challenge to theory and experiment

Abstract

The ability of theoretical chemists to quantitatively model the weak forces between organic molecules is being exploited to predict their crystal structures and estimate their physical properties. Evolving crystal structure prediction methods are increasingly being used to aid the design of organic functional materials and provide information about thermodynamically plausible polymorphs of speciality organic materials to aid, for example, pharmaceutical development. However, the increasingly sophisticated experimental studies for detecting the range of organic solid-state behaviours provide many challenges for improving quantitative theories that form the basis for the computer modelling. It is challenging to calculate the relative thermodynamic stability of different organic crystal structures, let alone understand the kinetic effects that determine which polymorphs can be observed and are practically important. However, collaborations between experiment and theory are reaching the stage of devising experiments to target the first crystallization of new polymorphs or create novel organic molecular materials.

The solid state forms of the sex hormone 17-β-estradiol

“…The crystal structures were modelled by the Ψ mol approach 28 of separating the lattice energy (U tot ) into the sum of the intermolecular interactions within the crystal (U inter ) and the conformational energy penalty for the conformational changes in the molecule from the most favourable isolated molecule structure (ΔE intra ). 28 Two separate CrystalPredictor2.2 (ref. 29) searches were carried out, with the hydroxyl group C4-C3-O1-H23 varying by up to 10°from either planar position, and the C13-C17-O2-H24 angle being a search variable.…”

Calculation of Diamagnetic Susceptibility Tensors of Organic Crystals: From Coronene to Pharmaceutical Polymorphs

“…The assumption that the charge distribution of a molecule is the same in isolation as in the crystal is often used for estimating electrostatic contributions to the lattice energy in CSP studies (the Ψ mol approach). 89 The tensor addition approximation may break down when the π electron density is more delocalized over adjacent molecules, for example, when a significant pressure is applied to a crystal. Another approximation inherent in the tensor addition method is the neglect of any local field effect, but as any induced magnetic fields generated by adjacent molecules are extremely small for diamagnetic crystals, this approximation should be valid in all cases.…”

The Role of Molecular Modeling & Simulation in the Discovery and Deployment of Metal-Organic Frameworks for Gas Storage and Separation

“…An annual workshop is held at the end of the year to disseminate and discuss the most innovative and successful approaches. 215 Within the realm of materials science, to spur developments and track progress in crystal structure prediction, 216 the CCDC holds a challenge to predict crystal structures of molecules. 217 To spur force field development, we envisage holding an open challenge to predict the adsorption isotherms of different gases in MOF struc-tures (holding the experimental MOF adsorption data secret).…”