The biochemistry of the para-sulfonato-calix[n]arenes has shown rapid development during the past ten years, the highly diverse biomedical applications of these molecules now include anti-viral, anti-thrombotic activities, enzyme blocking and protein complexation. The future is even more promising as para-sulfonato-calix[n]arenes have, now, been shown to have potential in the diagnosis of prion-based diseases. Their innocuous nature, as far as is known at present, may open up their future use in medications.

This review treats the biological properties of the various anionic calix[n]arenes, both as soluble forms and in the collodal state. The complexation of these molecules with amino-acids, peptides and proteins is discussed, as is their interaction with model membranes. The complexations with various Active Pharmaceutical Ingredients as complexes, for tamoxifen as solid state and colloidal structures, are treated in depth. Two sections deal with the direct biological action of the calix[n]arenes and their use as biosensors. A final section deals with the toxicity, in reality the lack of toxicity of the calix[n]arenes.

The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator–membrane and activator–carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene ≫ fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene ≈ coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator–carrier and activator–membrane interactions are discussed as supportive of arene-templated guanidinium–carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.

The water soluble p-sulfonatocalix[n]arenes (n = 4, 6 and 8) (1₄, 1₆ and 1₈) show glycosylaminoglycan (GAG) mimicry, being both active antithrombotics and modulators of lysyloxidase activity. In order to understand how these synthetic receptors interact with GAG receptor sequences, we have undertaken a study to thermodynamically characterize the binding of dipeptides and tripeptides bearing lysine or arginine residues by 1₄, 1₆ and 1₈ in aqueous buffer at pH 8.0 and 298.15 K. The association constants, enthalpies and entropies of complexation have been determined using titration microcalorimetry. The structure of the complexes in solution has been studied by ¹H NMR spectroscopy. Combining the microcalorimetric data, the binding shifts and the 2D experiments, the nature of the complexation may be clarified.

Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, the concentration of α-cyclodextrin used may be very high in these cases, and its toxic attributes have to be seriously considered. The objective of this study was to investigate the cytotoxicity of various, differently substituted α-cyclodextrin derivatives and determine relationship between the structures and cytotoxicity. Three different methods were used, viability tests (MTT assay and Real Time Cell Electronic Sensing on Caco-2 cells) as well as hemolysis test on human red blood cells. The effect of α-cyclodextrin derivatives resulted in concentration-dependent cytotoxicity, so the IC50 values have been determined. Based on our evaluation, the Real Time Cell Electronic Sensing method is the most accurate for describing the time and concentration dependency of the observed toxic effects. Regarding the cytotoxicity on Caco-2 cells, phosphatidylcholine extraction may play a main role in the mechanism. Our results should provide help in selecting those α-cyclodextrin derivatives which have the potential of being used safely in medical formulations.