Crown ethers biological mimics

Early work in the area of crown ether biological mimics was reported by Vogtle and coworkers (Tummler, 1977). These early compounds were made in an effort to duplicate natural ion carriers in the sense that they could complex biologically important ions for transport. The early, two-dimensional crowns (such as 5) and non-cyclic polyethers gave way to the three-dimensional ciyptands (6), which generally complexed ions more tightly but which lack the dynamics of podands, crown ethers, or lariat ethers. 

Electronic signals in nerve cells travel by means of metal-ion transport laterally in and out of the axon. Such transmembrane transport of ions is fundamental to cell biology, and attempts to mimic it artificially laid the foundation of supramolecular chemistry. Early studies in molecular recognition by Lehn in the 1970s explored the use of crown ethers as mimics of cyclic peptide ionophores like valinomycin, which bind cations selectively in their internal cavities. Natural ionophores act as antibiotics by upsetting the ionic balance across bacterial cell walls. 

Further interest is related to the design of adjustable hosts that permit to mimic cooperative interactions present in many biological functions, e.g., for the transport of sugars across cell membranes. In this respect, crown ethers have been functionalized with boronic acid units, e.g., compound 172, so that the... 

Hosts such as crown ethers and cryptands are useful as phase transfer agents and mimics of biological membrane transporting ionophores. 

Biological activity refers to a compound s ability either to alter or to mimic a living system or one of its components. A living system could be an entire animal, or even a cell in a Petri dish. Components of a living system would include organelles, proteins, or DNA. Crown ether compounds have been studied to determine their effects at these various levels of life. Crown ethers interact directly with such molecules as DNA and enzymes. Numerous crowns have also been tested for their toxic effects to various mammalian and bacterial cell lines, as well as animals including mice. 

Biological Ligands, p. 88 Crown Ethers, p. 326 Cryptands, p. 334 Enzyme Mimics, p. 546 lonophores, p. 760 Micelles and Vesicles, p. 861... 

As noted above, a goal of the lariat ether work was to develop eompounds that might function in a fashion similar to valinomycin. A dozen crown ethers, including two 1.3-xylyl-21-crown-6 macrocyclic poly ether 2-car-boxylic acid lariat ethers, were prepared and tested in vitro for biological activity. Several of the compounds showed activity and are thought to be functional mimics of ionophore antibiotics. 

Acyl transfer processes are of immense strategic and synthetic importance in synthesis and biology. In Fignre 12, the ability of peptidases snch as chymotrypsin to cleave amide bonds using a nncleophilic serine-195 residne to generate an activated acyl-enzyme intermediate was described. Numerous supramolecular structures have been designed that mimic these natural enzymatic acyl transfer processes, such as Lehn s crown ether/ammonium ion complexation... 

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