CH–π hydrogen bonds in biological macromolecules

Abstract

This is a sequel to the previous Perspective “The CH–π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates”, which featured in a PCCP themed issue on “Weak Hydrogen Bonds – Strong Effects?”: Phys. Chem. Chem. Phys., 2011, 13, 13873–13900. Evidence that weak hydrogen bonds play an enormously important role in chemistry and biochemistry has now accumulated to an extent that the rigid classical concept of hydrogen bonds formulated by Pauling needs to be seriously revised and extended. The concept of a more generalized hydrogen bond definition is indispensable for understanding the folding mechanisms of proteins. The CH–π hydrogen bond, a weak molecular force occurring between a soft acid CH and a soft base π-electron system, among all is one of the most important and plays a functional role in defining the conformation and stability of 3D structures as well as in many molecular recognition events. This concept is also valuable in structure-based drug design efforts. Despite their frequent occurrence in organic molecules and bio-molecules, the importance of CH–π hydrogen bonds is still largely unknown to many chemists and biochemists. Here we present a review that deals with the evidence, nature, characteristics and consequences of the CH–π hydrogen bond in biological macromolecules (proteins, nucleic acids, lipids and polysaccharides). It is hoped that the present Perspective will show the importance of CH–π hydrogen bonds and stimulate interest in the interactions of biological macromolecules, one of the most fascinating fields in bioorganic chemistry. Implication of this concept is enormous and valuable in the scientific community.