Non-covalent interaction via the reduced density gradient: Independent atom model vs experimental multipolar electron densities

The novel non-covalent interaction (NCI) descriptor proposed by Johnson et al. (J. Am. Chem. Soc. 2010, 132, 6498-6506) and based on the reduced density gradient (RDG), is applied to three molecular crystals, spanning a wide range of NCI classes. The key-aspect of this work is to contrast the NCI description obtained using the RDG of the electron density (ED) derived from single-crystal X-ray diffraction data with that calculated from the RDG of the corresponding Independent Atom Model (IAM) density. It is shown that the RDG isosurfaces obtained from the simpler, unperturbed model density are often able to highlight the same interactions revealed by the corresponding surfaces using the crystalline density, but differ systematically in size and are generally much less structured than these latter. A qualitative rationale for such differences is provided for the first time. Our results question the use of the simpler density model to study NCI in large biological systems. (c) 2012 Elsevier B.V. All rights reserved.