Calixarenes: paradoxes and paradigms in molecular baskets

Abstract

Calixarenes are [ln]metacyclophanes that can be prepared in one-flask syntheses from ceminp-alkylphenols and formaldehyde. Their history is a facet of phenol-formaldehyde chemishy which had its genesis in the nineteenth century laboratories of Adolph von Baeyer. Their structures were partially elucidated by Zinke and by Niederl in the 1940's, but incomplete data concerning their synthesis and purification created troubling paradoxes. As a result of the research by groups in Mainz, Parma, and St Louis in the late 1970s and early 1980s the paradoxes have been resolved and a paradigm has been created that has elicited widespread and increasing attention to these compounds. The conformational mobility of the calixarenes, which played a key role in the aforementioned paradox, has been well-studied both in the solid state and in solution. It can often be curtailed by appropriate substitution on the phenolic oxygen atoms which freezes the calixarene into a particular conformation.Calixarenes are especially amactive as cornplexing agents and enzyme mimics, because their basket-like shape allows them to act as hosts to guest molecules of appropriate size and character. As the result of the ease with which calixarenes can now be synthesized, functionalized, and conformationally fixed much effort is currently being devoted to such studies.Webster's dictionary defines paradox as "a tenet contrary to received opinion" and paradigm simply as "a model or pattern". Thomas Kuhn, a well known philosopher and historian of science, has given paradigm a broader and in some respects a less well defined meaning'. A scientific paradigm, he says, is created by an achievement that is sufficiently unprecedented to attract an enduring group of adherents away from competing modes of scientific activity and is sufficiently open ended to leave all sorts of problems for the redefined group of practitioners to resolve. It is Kuhn's thesis that the interplay of paradoxes and paradigms is responsible for what may seem to be an orderly progression in science but that in actual fact is a succession of fits and starts. Brief History of the Calixarenes:The present work concerns a set of paradigms that had their inception over a century ago in the laboratories of Adolf von Baeyer2. Baeyer was fascinated with colored compounds, and one of the types of reaction that he studied in his quest for new dyes was that of various phenols with aldehydes and ketones. In some cases he was successful in isolating and identifying the products, but when he took the simplest ingredients -namely, phenol itself and formaldehyde -he got a dark colored resinous tar that he despaired of characterizing and simply dispatched to the waste jar.Not until early in the twentieth century was this reaction finally tamed by Leo Baekeland who discovered that by using a small and controlled amount of base in the condensation of phenol and formaldehyde a commercially appealing material could be obtained. In 1907 he filed a patents on this process for making the material he called Bakel...

Molecular dynamics simulations of free energy and conformational transition rates of calix[4]arene in chloroform

“…16 This molecule consists of four phenol groups, each of which is connected to two neighboring phenols by methyl bridges located ortho to the hydroxyl group, see Fig. 1.…”

Encapsulation of Drug Molecules into Calix[n]arene Nanobaskets. Role of Aminocalix[n]arenes in Biopharmaceutical Field

“…Introduction of an organic solvent, for example, methanol or THF, to the aqueous solution shifts equilibrium toward the partial cone form . A chemical alternative is to isolate a particular conformer through controlled synthesis and is achieved by the attachment of propyl or larger groups to the CA skeleton, which provides “freezing” of the desired conformation through prevention of “oxygen‐through‐the‐annulus rotation.” Examples of synthesis of predetermined conformers are reported elsewhere …”

Influence of a Captured Solvent Molecule on the Isomerization Rates of Calixarenes

“…For this purpose, the carbon atoms of the phenol ring are numbered 1 through 6, starting at the carbon connected to the hydroxyl group, and the carbons of the methyl groups connecting rings are labeled a through d, with a and b at either side of the rotating ring. The orientation of the phenol ring is then described by the vectors a ) x 4 -x 1 …”