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.

Noncovalent synthesis using hydrogen bonding

Supramolecular chemistry has expanded dramatically in recent years both in terms of potential applications and in its relevance to analogous biological systems. The formation and function of supramolecular complexes occur through a multiplicity of often difficult to differentiate noncovalent forces. The aim of this Review is to describe the crucial interaction mechanisms in context, and thus classify the entire subject. In most cases, organic host-guest complexes have been selected as examples, but biologically relevant problems are also considered. An understanding and quantification of intermolecular interactions is of importance both for the rational planning of new supramolecular systems, including intelligent materials, as well as for developing new biologically active agents.

Binding Mechanisms in Supramolecular Complexes

Receptors for tetrahedral oxyanions

On the basis of many literature measurements, a critical overview is given on essential noncovalent interactions in synthetic supramolecular complexes, accompanied by analyses with selected proteins. The methods, which can be applied to derive binding increments for single noncovalent interactions, start with the evaluation of consistency and additivity with a sufficiently large number of different host–guest complexes by applying linear free energy relations. Other strategies involve the use of double mutant cycles, of molecular balances, of dynamic combinatorial libraries, and of crystal structures. Promises and limitations of these strategies are discussed. Most of the analyses stem from solution studies, but a few also from gas phase. The empirically derived interactions are then presented on the basis of selected complexes with respect to ion pairing, hydrogen bonding, electrostatic contributions, halogen bonding, π–π-stacking, dispersive forces, cation−π and anion−π interactions, and contributions f...

Experimental Binding Energies in Supramolecular Complexes

Hydrogen bonding is a directional and moderately strong intermolecular force. Compounds that present multiple hydrogen-bond donor and acceptor groups have proven to be extremely important in creating new self-assembled structures. A review of several classes of organic compounds capable of multiple hydrogen-bond recognition is presented with a focus on the factors that contribute to complex stability.

Heteroaromatic Modules for Self-Assembly Using Multiple Hydrogen Bonds

NMR Shift titrations with 2,6-diacyldiaminopyridines as well as with the parent benzene derivative and barbiturates indicate strong hydrogen bond attenuation by steric hindrance, by flexible side chains, and by chloroform as solvent. Analysis of unhindered associations and of corresponding host-guest complexes reported in the literature shows a linear correlation of complexation free energy ΔG° with the number n of hydrogen bonds for n > 1, which amounts to ΔG° = (5 ± 1) kJ/(mol · n) in CDCl3; this value is expected to increase in carbon tetrachloride to ΔG° ≈ 10 kJ/(mol · n) as judged by extrapolation from 2 measurements.

Solvent and Structural Effects on Hydrogen Bonds in Some Amides and Barbiturates. An Additive Scheme for the Stability of Corresponding Host‐Guest Complexes

Ravindra K. Juneja

Papers

Solvent and Structural Effects on Hydrogen Bonds in Some Amides and Barbiturates. An Additive Scheme for the Stability of Corresponding Host‐Guest Complexes