Some of you may be familiar with the term “halogen bonding”. In analogy to hydrogen bonding, this weak interaction occurs between an electron donor, such as nitrogen, and a halogen (Cl, Br, I). The halogen acts as an electrophile.
This is possible because the halogen has a region of positive partial charge at its tip, the so-called sigma-hole, as shown by calculations (doi:10.1007/s00894-006-0130-2). The group of Resnati and Metrangolo in Milan have used this interaction to construct a variety of polymeric chains and networks for crystal engineering. As they discuss in their current Science paper (doi:10.1126/science.1162215), it also plays an important role for drug design, which I am particularly interested in. Many drugs on the market are halogenated aromatics. The exact role of the halogen for binding is not always known, since often it was introduced in order to tune the hydrophobicity of the compound. I suspect that in many instances, halogen bonding to a backbone carbonyl oxygen could be of importance.
Clearly, more work is required to further investigate halogen bonding in a biological context. If people want to incorporate this kind of interaction into rational drug design or crystal engineering, good quantitative models will be needed.