Macrocyclic glycoclusters. Self-aggregation and phosphate-induced agglutination behaviors of calix[4]resorcarene-based quadruple-chain amphiphiles with a huge oligosaccharide pool

Macrocyclic glycocluster compounds 2(n) (n = 2-7) with four alkyl (undecyl) chains and eight oligosaccharide moieties on the opposite sides of the calix[4]resorcarene macrocycle are prepared from the reactions of the corresponding octaamine derivative with maltooligosaccharicle lactones. Combined evidence from dynamic light scattering (DLS), gel permeation chromatography (GPC), and transmission electron microscopy (TEM) indicates that they form small micelle-like nanoparticles (d congruent to 3 nm) in water. In the presence of Na2HPO4/NaH2PO4, nanoparticles are agglutinated with phosphate ions as a glue to grow in size up to 60-100 nm, as revealed by DLS as well as microscopy (TEM and AFM). The phosphate-induced agglutination processes can be followed by surface plasmon resonance (SPR). Amphiphile 2 is readily immobilized on the hydrophobized sensor chip of SPR to give a closely packed monolayer with oligosaccharide moieties exposed to bulk water. While there is no further adsorption of 2(n) on the resulting monolayer, this does occur when the latter is pretreated with the phosphate salts, ultimately giving rise to a multilayer upon repeated treatment of the chip with 2(n) and Na2HPO4/NaH2PO4 in an alternate manner. Kinetic analyses show that the phosphate-mediated inter(saccharide) interactions in terms of rate and affinity are markedly dependent on the oligosaccharide chain lengths (n), becoming more favorable with increasing n's. The novel aggregation and agglutination behaviors observed are discussed in terms of immobilizable and irreversible micelles on the basis of the cone-shaped structure of quadruple-chain amphiphile 2n having a huge saccharide pool and the efficiency of multiple hydrogen bonding therein. The unique intermolecular binding properties of compound 22 and analogues so far reported are reviewed in light of the present finding.