Single crystals of a lipophilic G-quadruplex formed by 5'-tert-butyl-dimethylsilyl-2',3',-di-O-isopropylidene G 2 were obtained from a CH3CN solution containing potassium picrate and cesium picrate. The X-ray structure showed that 16 units of G 2 and 4 equiv of alkali picrate form the lipophilic G-quadruplex. The quadruplex has a filled cation channel, with three K+ ions and one Cs+ ion located along its central axis. The quadruplex is formed by a pair of head-to-tail (G 2)(8)-K+ octamers. Both octamers use eight carbonyl oxygens to coordinate K+. The two (G 2)(8)-K+ octamers are of opposite polarity, being coaxially stacked in a head-to-head orientation. A Cs+ cation, with an unusual coordination geometry, caps the cation channel. The Cs+ is coordinated to four acetonitrile solvent molecules in an eta(2)-fashion. Within an octamer the two tetramers are stacked so that they are 3.3 Angstrom apart and twisted by 30 degrees. A second stacking interaction is defined by the bend-to-head arrangement between the two (G 2)(8)-K+ octamers. This stacking, with a 90 degrees twist, positions the exocyclic amines of the central two quartets so that both exocyclic NH2(B) protons can hydrogen bond to the picrate anions that rim the quadruplex equator. The four picrates form an anionic belt that wraps around the cation channel. The sugars are well ordered in the structure. Circular dichroism spectra indicate that the G-quadruplex retains its helical structure in chlorinated solvents.