Mimicking Biological Recognition: Lessons in Binding Hydrophilic Guests in Water

Abstract

Selective molecular recognition of hydrophilic guests in water plays a fundamental role in a vast number of biological processes, but synthetic mimicry of biomolecular recognition in water still proves challenging both in terms of achieving comparable affinities and selectivities. This Review highlights strategies that have been developed in the field of supramolecular chemistry to selectively and non‐covalently bind three classes of biologically relevant molecules: nucleotides, carbohydrates, and amino acids. As several groups have systematically modified receptors for a specific guest, an evolutionary perspective is also provided in some cases. Trends in the most effective binding forces for each class are described, providing insight into selectivity and potential directions for future work.

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

“…Many other examples exist, rendering these compounds one of the largest and structurally diverse receptor classes for anions in water. [ 19 , 20 , 21 , 22 , 27 ]…”

“…Charge‐assisted hydrogen bonds are also operative in Schmuck's guanidiniocarbonyl pyrrole (GCP)‐based receptors, which primarily serve to bind carboxylates or phosphates. [ 27 , 49 ] A guanidinium moiety serves in these systems as the primary binding site that in itself has unusual properties in water. [50] Guanidinium ions are protonated at pH values up to 12 due to their high p K a , for example, and feature a seam of hydrogen bond donors along the edge of their planar structure.…”

“… [98] Accordingly, it is often problematic to limit the discussion of the thermodynamics of complex formation in aqueous buffers to receptor‐substrate interactions and solvation effects alone. [27] …”

“…This work, which demonstrates the potential use of such cyclophanes in biomedicinal applications, has recently been reviewed. [27] …”

“…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.…”