Raman scattering (RS) was used as a powerful, efficient, and sensitive technique for studying intermolecular interactions between an organic ligand adsorbate and a metallic substrate. Functionalization of titanium (TiO 2 [Formula: see text]Ti) surfaces was performed using lysine (Lys) as adsorbate and later developing a hydroxyapatite (HA) layer onto this functionalized surface. The functionalization process was performed at different pH values of the interacting chemical species. Chemisorption onto the TiO 2 Ti substrates through the Lys carboxylic group was demonstrated spectroscopically. Analysis of vibrational spectra showed that the CH side chain of Lys was relatively distant from the (TiO 2 [Formula: see text]Ti) surface, preventing direct contact with the surface. Additionally, the signals corresponding to the unbound [Formula: see text]-NH 2 group indicate that it is available for additional complexation. In vitro bioactivity of the Lys–TiO 2 [Formula: see text]Ti surface was achieved by developing an HA layer onto already functionalized TiO 2 [Formula: see text]Ti surfaces at various pH values. Spectroscopic data using the spectral markers of HA and Lys provided a decisive role in establishing the necessary baseline data for evidencing the intermolecular bonding. The functionalized TiO 2 [Formula: see text]Ti surface reactivity is linked to the specific intermolecular interactions of –COO − (pH 7.0) with Ca[Formula: see text] ions, as well as the –COOH (pH 2.0 and 12.0) groups of Lys, with the –OH groups of PO[Formula: see text] belonging to HA.