The guanidinium group of arginine (Arg) in proteins has been observed to bind oxo anions such as carboxylate, phosphate, superoxide, etc. Such interactions are essentially hydrogen bonds and are expected for other basic amino acids such as lysine (Lys). However, recent findings on oxygen activated enzymes indicate that metal-coordinated anions are specifically bound to the Arg guanidinium group. To shed light on this, we carried out thermodynamic (pH titrations at various temperatures (5, 25, 37°C) and 0.1M KNO 3 ), spectral (absorption and circular dichroism (CD)), and crystal structural studies on Cu(II)-dipeptide (L) systems (L = ArgAsp, ArgGlu, GlyAsp, GlyGlu, LysAsp, LysGlu) where intramolecular interactions between the Arg guanidinium group and the carboxylate group of Asp and Glu are possible.The absorption spectra of Cu(II)-L in aqueous solution at various pH showed that they have the same coordination structures as those of Cu(II)-GlyGly complex species (CuL, CuLH - 1 , CuLH - 2 , CuLH - 3 ). The CD magnitude change for Asp containing systems indicated an additional coordination by the ω-carboxylate group in the apical position. The apical coordination was inferred to be dependent on the structure and solvent, and to become gradually weaker from CuLH - 1 to CuLH - 3 and from H 2 O to 50% aqueous dioxane.The interactions between the Arg guanidinium and the Glu carboxylate groups were revealed in the crystal structure of [Cu(ArgGlu)H - 1 ] 4H 2 O (FIGURE 1), where a guanidinium group is involved in the bondings with the two oxygens of α-COO and one oxygen of γ-COO of neighboring complex molecules. These weak bonds probably asist the unusual coordination that the Cu(ArgGlu)H - 1 complex is bound to γ-COO - of the adjacent complex, forming an infinite chain of complexes. The solution equilibria of the Cu(II)-L systems showed the preference of the complex formation due to the intramolecular interaction, whose complex stabilizing effect in CuLH - 1 was in the order of L, ArgAsp ArgGlu > LysAsp LysGlu. Arg in the complex stabilized the interaction by the ΔS contributions. The interactions in these complexes were supported by the CD spectra, whose magnitudes deviated from the additivity described as Δ C u - A B = Δ C u - A G l y + Δ C u - G l y B . Solvent dependence of the CD additivity showed the deviations were due to the polar interaction. Large deviation from the additivity observed for the Cu-(ArgAsp)H - 1 complex in 1M KNO 3 suggested an unusual bonding between the Arg guanidinium and Cu coordinated Asp carboxylate groups. That the bonding is preferred even at high ionic strength would mean necessary for the enzyme reaction.The model studies on the Cu-dipeptide systems demonstrated the preference of the combination of the Arg guanidinium group and Cu coordinated oxygen anion.