Ionophores are antibiotics that induce ion transport across nutiirul and artlficial membrane..s. The specijic,fiinction o f a given ionophore depends upon its selectivity and the kinetics qf ion capture, transport, and release. Systematic studies of complesed and uncomplesed .forms of linear and cyclic ionophores provide insight into moleczilar mechanisms of ion captiire and release and the basis for ion selectivity. The cyclic dodecadepsipeptide valinomycin, cyclo[ (-L-Val-0-Hyi-0-VU~-L-LUC)~-1, transports potassium ions across ce/lu/ar membrane bilayers selectively. The x-ray crystallographic and nmr spectroscopic data concerning the structures of .Va', K', and Bu'~ complexes are consistent and provide a rationule,for the K' selectivity of valinomycin. Three significantly different conformations of valinomycin are observed in anhvdrous crystals, in hydrated crystals grown jiom dimethylsufijxide, and in crystals grown from dioxane. Each ofthese conformations suggests a diferent mechanism of ion capture. One of the observed conformations has an elliptical structure stabilized by,four 4 c 1 intramolecular hydrogen bonds and two 5 +-I hydrogen bonds. Ion capture Coldd be readily achieved by disruption ofthe 5 c 1 hydrogen bonds to permit coordination to a potassium ion entering the cavity. The conformation.found in crystals obtained.fiom dimethyl siilfoside is an open flower shape having three petals and threr 4 c 1 hydrogen bonh. Complesation could proceed by a closing up ofthe three petals of the flower around the desolvating ion. In the third,form, water molecules reside in the central cavity of a bracelet structure having six 4 c 1 hydrogen bonds. Two ofthese bracelets stack over one another with their valine-rich,fuces surrounding a dioxane molecule. The stacked molecules,form a channel approximatel-v 20 k in length, suggesting that under certain circumstances valinomycin might function as a channel. A series of analogues of mlinomycin differing in ring composition and size have been synthesized and their transport properties tested. Peptide substitution and chiral variation in the dodecadepsipeptide can result