Classical molecular dynamics simulations and density functional theory calculations are performed to obtain insights about the attachment of the copper(II) ion to the lowest generation poly(amido-amine) dendrimer, G0-OH, in aqueous solutions. Various initial configurations of the ion relative to the dendrimer sites are tested and it is concluded that both the solvent as well as-in a lesser degree for low generation dendrimers-the folding of the dendrimer branch play an important role in copper(II) ion complexation. The presence of solvent and branch folding retain the ion close to the atomic binding sites consisting mainly of amide oxygen as well as hydroxyl oxygen but also tertiary amine nitrogen. A discussion of currently available experimental results in Cu(II) complexation in larger generation dendrimers is provided. © 2005 American Chemical Society.