Sensing A Paradigm Shift in the Field of Molecular Recognition: From Selective to Differential Receptors

Abstract

Molecular recognition has evolved from a science designed to understand biological systems into a much more diverse area of research. While work continues to elucidate “nature's tricks” with respect to intermolecular interactions, much attention has turned to the perspective that molecular recognition, by design, can lead to new technologies. Applications ranging from molecular sensing to information storage and even working molecular machines have been envisioned. This review will highlight a few historical hallmarks of molecular recognition oriented at studying the basic science of intermolecular interactions, but then detail recent advances in molecular recognition aimed towards applications in the field of molecular sensing. Rational design can be used to create synthetic receptors with a good deal of predictability and selectivity, and many signal transduction mechanisms exist for converting these receptors into sensors. This is the first topic discussed. The concept of “differential” or “generalized” sensing is then presented, where one uses an array of sensors that do not necessarily conform to the “lock and key” principle. This approach to sensing is inspired by the mammalian senses of taste and smell, which we briefly describe. To mimic senses of taste and smell, one is naturally led to the use of combinatorial libraries, a direction of research that has seen continued growth over the past few years. We summarize the current state of the art in synthetic combinatorial receptors/sensors, and then predict a future direction that the field of molecular recognition will possibly take. The review is not meant for the specialist, but instead for a general audience. It does not present a highly detailed analysis of each individual topic: synthetic receptors, sensors, olfaction/gustation, and combinatorial receptors/sensors. Instead, this review shows how all these fields complement each other and fit together to create sensing devices. Our conclusion is that specific analyte sensing, differential sensing, and combinatorial chemistry can and will be combined to create sensor arrays, and give the subfield of molecular recognition that uses synthetic systems a bright future in this type of sensing scenario.

Cucurbit[n]uril Analogues

“…[44][45][46] The scientific insights gained from fundamental studies of non-covalent interactions have been of practical value in a wide range of applications including chromatographic stationary phases, sequestration of contaminants from solution, and the development of catalysts, chemical sensors, and new drugs. All of these applications require the availability of low molecular weight receptors, [47][48][49] natural or non-natural oligomers and polymers, 50,51 or solid state materials [52][53][54] that interact with their analytes in high affinity, highly selective binding processes. In response, supramolecular chemists have designed, synthesized, and evaluated the recognition properties of a wide variety of non-natural receptors -including cyclodextrins, calixarenes, cyclophanes, crown ethers, and many others -that display remarkable affinity and selectivity ( Figure 2).…”

Probing optical recognition of metal ions with employment of cationic dye-calix[4]arene supramolecular complexes

“…2 For example, fluorogenic calix [4]arene derivatives with dansyl units incorporated in the pendent proton-ionizable groups were found to provide selective and efficient optical recognition of such heavy toxic metal ions as Hg 3b,3e However, this methodology has definite limitations. Thus, it requires synthetic efforts for covalent immobilization of a dye fragment to the metal receptor.…”

“…Such an approach is attractive since not only it eliminates extra steps in synthesis, but it also allows for employment of combinatorial method: variation of dyes with the same ligand (or vice versa) may create libraries of ion-sensitive ensembles. 4 Functionalized calixarenes -macrocyclic receptors containing pendent functional groups on the π-electron-rich aromatic metacyclophane framework -are capable of various intermolecular interactions, which determines their propensities for "hosting" both metal cations 5 and organic molecular and ionic species, in particular, dyes. 6 This makes calixarenes appropriate ligands for exploring this alternative approach to sensing of metal ions.…”

“…8 At the same time, only limited information is available for such competitive optical sensing of spherical metal cations with involvement of host-guest complexes of calixarenes with dyes. Thus, Nau et al found that in complexation with a calix [4]arene containing four upper-rim sulfonate groups, different metal ions can displace encapsulated in the host cavity 2,3-diazabicyclo[2.2.2]oct-2-ene, which produces a sharp increase of this molecule fluorescence. 9 Such a reaction may be presented schematically as shown in Figure 1.…”

“…As a result, a ternary complex dye-calixarenemetal ion will be formed. In this paper, we present a study of complex formation of calix [4] Proton-ionizable calix [4]arenes:…”