Non-covalent interactions revealed by mapping the energy density on the reduced density gradient isosurfaces

Non-covalent interactions (NCI) are crucial in biology (protein-drug recognition) and in the design of new materials (self-assembly). A novel electron density (ED)-based NCI descriptor - which exploits a key quantity in DFT, the Reduced Density Gradient s(r) - was recently proposed by Johnson et al. [1]. They demonstrated that (i) NCI can be investigated in R3 by low-s isosurfaces, and that (ii) the ED multiplied by the sign of its second largest curvature can classify various kinds of NCI as allegedly attractive or repulsive. We propose here a new approach, in which the total energy density, H(r), is mapped onto low-s isosurfaces. We work on the 22 molecular test case dimers proposed by Hobza et al. [2], showing that H(r) is able to distinguish among different NCI (hydrogen-bonds, van der Waals, C-H···?) and to rank their relative importance. In addition, as low-s isosurfaces encompass regions characterized by low and smoothly varying ED, we find that this approach is suitable even in conjunction with the approximate Abramov's functional [3] that allows computing H(r) directly from experimental (X-ray) ED's. References [1] E. R. Johnson, et al., J. Am. Chem. Soc. 132 (2010) 6498-6506. [2] P. Juracka, et al., Phys. Chem. Chem. Phys. 8 (2006) 1985-1993. [3] Y. A. Abramov, Acta Cryst. A53 (1997) 264-272.