We present a mechanism for the selectivity of covalent/electrostatic binding of the Cr(III) ion to collagen, mediated by the kosmotropicity of the anions. Although a change in the long-range ordered structure of collagen is observed after covalent binding (Cr(III)-OOC) in the presence of SO 4 2− at pH 4.5, the ν sym (COO −) band remains intense, suggesting a relatively lower propensity for the Cr(III) to bind covalently instead of electrostatically through Cr(H 2 O) 6 3+. Replacing SO 4 2− with Cl − reduces the kosmotropic effect which further favors the electrostatic binding of Cr(III) to collagen. Our findings allow a greater understanding of mechanism-specific metal binding in the collagen molecule. We also report for the first time, surfaceenhanced Raman spectroscopy to analyze binding mechanisms in collagen, suggesting a novel way to study chemical modifications in collagen-based biomaterials.