The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl-2(N-1-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (A beta(28)) and the resulting {Ru(CO)(3)}(2+) peptide adduct was investigated by a variety of biophysical methods. H-1 NMR titrations highlighted a selective interaction of {Ru(CO)(3)}(2+) with A beta(28) histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of A beta(28); electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when I was reacted with A beta(42). The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.