We report the first direct solution NMR detection of the alkali metal cations (Na-23(+), K-39(+), and Rb-87(+)) residing inside G-quadruplex channel structures formed by guanosine 5 '-monophosphate and a DNA oligomer, d(TG(4)T). In solution, these channel alkali metal cations are tightly bound to the G-quadruplex structure and have been considered to be "invisible" to NMR spectroscopy for many years. Our finding that it is possible to directly observe these alkali metal cations by NMR spectroscopy provides a new tool for studying cation binding affinity and dynamics in G-quadruplex DNA. (c) 2005 Elsevier Inc. All rights reserved.