Molecular Recognition Mediated by Hydrogen Bonding in Aqueous Media

Abstract

Hydrogen bonding is a key governing force in molecular recognition, notably in biological systems. While it has been studied and exploited by supramolecular chemists for many years, most of this work has been conducted in organic solvents. Investigations in water, the biological solvent, have proceeded more slowly, largely because the interaction is weakened by solvation and less easy to detect. Recently it has become appreciated that the problems should be addressed, and work towards the deployment of H‐bonding in water has accelerated. This Minireview discusses a range of synthetic receptors designed to bind organic molecules in aqueous media by combining hydrogen bonding with hydrophobic interactions. Some of these systems are capable of high affinities and selectivities, raising the hope of biomedical applications in the near future.

When Molecules Meet in Water‐Recent Contributions of Supramolecular Chemistry to the Understanding of Molecular Recognition Processes in Water

“…For the same reason, hydrogen bond formation between synthetic receptors and their substrates generally takes place in cavities well shielded from the surrounding solvent. [28] These cavities not only feature hydrogen bond donors and/or acceptors along their inner surfaces but often also hydrophobic residues that can mediate further types of interactions and, more importantly, prevent the efficient hydration of the converging polar groups. Dehydration is thus facilitated, which causes binding to benefit from the release of cavity water.…”

“…Finally, hydrogen bonds are stronger in an environment that has a lower permittivity than water, and hydrogen bonds in proteins are therefore mostly buried within the folded protein chain. For the same reason, hydrogen bond formation between synthetic receptors and their substrates generally takes place in cavities well shielded from the surrounding solvent [28] . These cavities not only feature hydrogen bond donors and/or acceptors along their inner surfaces but often also hydrophobic residues that can mediate further types of interactions and, more importantly, prevent the efficient hydration of the converging polar groups.…”

“…Examples are cyclodextrins,[ 17 , 18 ] macrocyclic polyamines,[ 19 , 20 , 21 , 22 ] and cucurbiturils. [ 23 , 24 ] Some aspects of supramolecular chemistry in water are therefore known for some time,[ 9 , 25 ] but with the increasing interest in developing receptors for practical applications,[ 26 , 27 , 28 , 29 ] many of which require functioning systems in water, the interest in deciphering the principles of molecular recognition in water has grown considerably.…”