This article analyzes the interaction between cobalt cations and lysine both theoretically and experimentally. The influence of d orbital occupation in Co+/2+ cations and the side chain of lysine on the relative stability of the different coordination modes was studied by means of theoretical methods. The structure and vibrational frequencies were determined using the B3LYP and BHLYP methods. Single-point calculations were also carried out at the CCSD(T) level. For both systems, Co+-lysine and Co 2+-lysine, the most stable structure results from the interaction of neutral lysine to the metal cation through the two amino groups and the carbonyl oxygen, the ground electronic state being a 3A in the case of Co+ and 4A for the Co2+ system. This is in contrast to that found for Co2+ interacting with glycine in which the most stable structure has the amino acid in its zwitterionic form, which points out the importance of the side chain. © 2008 American Chemical Society.