Alzheimer's disease (AD) patients show abnormally high concentrations of Cu2+ in the amyloid beta plaques. This invokes that Cu2+ might play a crucial role in the onset of AD. The last few decades of research have also shown that Cu2+ plays a significant role in the aggregation of A beta plaques in the brain and the generation of oxidative stress. Because the crystal structures of Cu-A beta are yet to be obtained, there are various proposed models for the Cu2+ coordination environment of A beta peptides. In this study, we have used the truncated hydrophilic part of the native A beta peptide to probe the Cu2+ coordination site of the peptide, using a combination of spectroscopy and exogenous ligand-binding studies. It is evident from our study that A beta(1-16) binds 1 equiv of Cu2+ and yet shows an equilibrium between two species with a pK(a) of similar to 8.1. Ligand-field analysis of absorption and circular dichroism spectroscopy data indicates five-coordinate geometry for both components. We investigate the effect of azide and 8-hydroxyquinoline binding to Cu-A beta and demonstrate the presence of a water-derived ligand and a second exchangeable ligand coordinated to copper at physiological pH, along the equatorial plane of a square-pyramidal active site.