C–H⋯O and other weak hydrogen bonds. From crystal engineering to virtual screening

Hydrogen bonds, X–H⋯A, formed by weak donors (X = C) and acceptors (A = π system) were generally dismissed as being of little consequence before and even during the 1970s. This situation changed in the early 1980s, and during the two following decades they were implicated as being significant in many small molecule crystal structures, and also in solution. Today, knowledge gained about these interactions is being used to understand the structure of biomolecules with implications for structure based drug design.