Solution geometries and lipophilicity patterns of alpha-cycloaltrin

Detailed analysis of the conformational features of alpha-cycloaltrin (1) i n aqueous solution by temperature dependent H-1 and C-13 NMR studies, toget her with molecular dynamics simulations, reveal that the six altropyranose units are in a complex dynamic equilibrium within the C-4(1) reversible arr ow S-0(2) reversible arrow C-1(4) pseudorotational turntable. This gives ri se to a large number of macrocyclic conformations, ranging from a disk-shap ed molecule with a hydrophobic central hole (alternating C-4(1)/C-1(4) form la) to a torus form of the macrocycle with an equally hydrophobic through- going cavity (all skew-boat form 1b). Constrained MD simulations throw ligh t on the conformational transitions between these two extreme forms (1a rev ersible arrow 1b). Flexure of one altropyranoid chair into the skew-boat-S- 0(2) form forces adjoining altropyranoid units to follow suit, thereby elic iting a successive, synergistic "rolling around" within the, on average, el liptical macrocycle. Thus, alpha-cycloaltrin is the first thoroughly flexib le cyclooligosaccharide and can be used to probe the induced-fit mode of gu est-host interactions.