ИСТИНА

Halogen bonding (XB), defined as a weak non-covalent attractive interaction of heavy halogens (Cl, Br and I) and Lewis donors, has emerged during the last decade as a promising avenue for optimizing intermolecular interactions in drug design. Lewis donors can be N, O atoms in molecules as well as aromatic π-systems. Most mentions of XB however come from retrospective analysis of X-ray crystallographic data, as well as results of high throughput screening in hit finding and lead optimization activities. For now only a few examples exist, which demonstrate the use of XB in completely prospective design and development. To guide the rational use of XB, first, its origin and traits should be well understood, and, second, a set of appropriate tools should be available at the disposal of a researcher to model it. We overview different approaches to halogen bonding modeling, their accomplishments and relative prospects. We also describe a set of methods developed in our group for description of XB, including the use of multipole expansion up to quadrupole around heavy halogens and its proper substitute, approximated by point off-atom charges, for application in classical force field modeling packages. The areas of future development are outlined.