Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.

The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low-molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution, and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density.

Revisiting a Historical Concept by Using Quantum Crystallography: Are Phosphate, Sulfate and Perchlorate Anions Hypervalent?

There are many examples of atoms in molecules that violate Lewis' octet rule, because they have more than four electron pairs assigned to their valence. These atoms are referred to as hypervalent. However, hypervalency may be regarded as an artifact arising from Lewis' description of molecules, which is based on the assumption that electrons are localized in two-center two-electron bonds and lone pairs.

Linear MgCp* vs Bent CaCp*: London Dispersion, Ligand-Induced Charge Localizations, and Pseudo-Pregostic C-H···Ca Interactions.

In the family of metallocenes, MgCp* (Cp* = pentamethylcyclopentadienyl) exhibits a regular linear sandwich structure, whereas CaCp* is bent in both the gas phase and solid state. Bending is typically observed for metal ions which possess a lone pair. Here, we investigate which electronic differences cause the bending in complexes lacking lone pairs at the metal atoms.

The Elusive Structural Origin of Plastic Bending in Dimethyl Sulfone Crystals with Quasi-isotropic Crystal Packing.

Bending in molecular crystals is typically associated with the anisotropy of intermolecular interactions. The intriguing observation is reported of plastic bending in dimethyl sulfone, which exhibits nearly isotropic crystal packing and interaction topology, defying the known structural models of bending crystals. The origin of the bending phenomenon has been explored in terms of intermolecular interaction energies, experimental X-ray charge density analysis, and variable temperature neutron diffraction studies.

Energy frameworks: insights into interaction anisotropy and the mechanical properties of molecular crystals.

We present an approach to understanding crystal packing via 'energy frameworks', that combines efficient calculation of accurate intermolecular interaction energies with a novel graphical representation of their magnitude. In this manner intriguing questions, such as why some crystals bend with an applied force while others break, and why one polymorph of a drug exhibits exceptional tabletability compared to others, can be addressed in terms of the anisotropy of the topology of pairwise intermolecular interaction energies. This approach is applied to a sample of organic molecular crystals with known bending, shearing and brittle behaviour, to illustrate its use in rationalising their mechanical behaviour at a molecular level.