Noncovalent Synthesis Using Hydrogen Bonding

Hydrogen bonds are like human beings in the sense that they exhibit typical grouplike behavior. As an individual they are feeble, easy to break, and sometimes hard to detect. However, when acting together they become much stronger and lean on each other. This phenomenon, which in scientific terms is called cooperativity, is based on the fact that “1+1 is more than 2”. By using this principle, chemists have developed a wide variety of chemically stable structures that are based on the reversible formation of multiple hydrogen bonds. More than 20 years of fundamental studies on these phenomena have gradually developed into a new discipline within the field of organic synthesis, and is nowadays called “noncovalent synthesis”. This review describes noncovalent synthesis based on the reversible formation of multiple hydrogen bonds. Starting with a thorough description of what the “hydrogen bond” really is, it guides the reader through a variety of bimolecular and higher order assemblies and exemplifies the general principles that determine their stability. Special focus is given to reversible capsules based on hydrogen‐bonding interactions that exhibit interesting encapsulation phenomena. Furthermore, the role of hydrogen‐bond formation in self‐replicating processes is actively discussed, and finally the review briefly summarizes the development of novel materials (nanotubes, liquid crystals, polymers, etc.) and principles (dynamic libraries) that recently have emanated from this intriguing field of research. The combined strength of weak interactions at the molecular level can be used to build thermodynamically stable structures with exciting new properties. This review describes the characteristic traits of a new type of organic synthesis which uses the formation of hydrogen bonds between a H‐bond donor (D) and an acceptor (A) group, such as in the AAD⋅DDA module 1‐methylcytosine⋅9‐methylguanine (see scheme).