Crown ethers are of enormous interest and importance in chemistry, biochemistry, materials science, catalysis, separation, transport and encapsulated processes, as well as in the design and synthesis of various synthetic systems with specific properties, diverse capabilities, and programmable functions. Classical crown ethers are macrocyclic polyethers that contain 3-20 oxygen atoms separated from each other by two or more carbon atoms. They are exceptionally versatile in selectively binding a range of metal ions and a variety of organic neutral and ionic species. Crown ethers are currently being studied and used in a variety of applications beyond their traditional place in chemistry. This review presents additional applications and the ever-increasing biomedical potentials of these intriguing compounds, with particular emphasis on the prospects of their relevance as anticancer agents. We believe that further research in this direction should be encouraged, as crown compounds could either induce toxicities that are different from those of conventional antitumor drugs, or complement drugs in current use, thereby providing a valuable adjunct to therapy.

The present paper demonstrates the antiproliferative ability and structure-activity relationships (SAR) of 14 crown and aza-crown ether analogues on five tumor-cell types. The most active compounds were di-tert-butyldicyclohexano-18-crown-6 (3), which exhibited cytotoxicity in the submicromolar range, and di-tert-butyldibenzo-18-crown-6 (5) (IC50 values of approximately 2 microM). Also, 3 and 5 induced marked influence on the cell cycle phase distribution--strong G1 arrest, followed by the induction of apoptosis. A computational SAR modeling effort offers insight into possible mechanisms of crown ether biological activity, presumably involving penetration into cell membranes, and points out structural features of molecules important for this activity. The results reveal that crown ethers possess marked tumor-cell growth inhibitory activity, the extent of which depends on the characteristics of the hydrophilic macrocylic cavity and the surrounding hydrophobic ring. Our work supports the hypothesis that crown ether compounds inhibit tumor-cell growth by disrupting potassium ion homeostasis, which in turn leads to cell cycle perturbations and apoptosis.

Three dissymmetric gemini surfactants (abbreviated as 12-s-14) in which n-dodecyldimethylammonium bromide and n-tetradecyldimethylammonium bromide are connected at the polar headgroups by a flexible -(CH2)s-spacer (s ) 2, 6, or 10) have been synthesized. The influence of the spacer length on the structural and thermal properties of 12-s-14 surfactants was investigated by means of IR and NMR spectral analysis, X-ray diffraction, thermogravimetry, differential scanning calorimetry, and polarizing optical microscopy. Geminis with s ) 2 or 10 form monolayers in which two alkyl chains are in the trans configuration, while the gemini with s ) 6 forms interdigitated bilayers with two alkyl chains in the cis configuration with respect to the spacer. All compounds exhibited a complex polymorphism and thermotropic mesomorphism from the stable crystalline form to the liquid crystalline phases of smectic type. The number of thermal phase transitions and the sequence of phases are markedly affected by the spacer length; that is, they depend on the configuration of the two alkyl chains with respect to the spacer.

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