Modulation of an n ->pi* interaction with alpha-fluoro groups

Noncovalent interactions play an essential role in biological and chemical processes. In the main chain of common protein secondary structures, the lone pair (n) of a carbonyl oxygen is delocalized into the antibonding orbital (pi*) of the subsequent carbonyl group. Herein, experimental and computational data reveal that this n ->pi* interaction can be attenuated by the inductive electron withdrawal of one or two alpha-fluoro groups in the donor. The steric effect of three alpha-fluoro groups, however, overcomes the inductive withdrawal. These data evoke a means to modulate the n ->pi* interaction in peptides, proteins, and other systems.