The interactions between DNA purines (guanine and adenine) and the ruthenium complex Ru(NO)(NO(3))(3) were studied within nanostructured silica matrices prepared by a two-step sol-gel process. By infrared analysis in diffuse reflectance mode, it was proved that encapsulation induces a profound modification on the complex, whereas guanine and adenine preserve their structural integrity. The complex undergoes nitrate ligand exchange and co-condenses with the silica oligomers, but the nitrosyl groups remain stable, which is an unusual behavior in Ru nitrosyl complexes. In turn, the doping molecules affect the sol-gel reactions and eventually the silica structure as it forms: the complex yields a microporous structure, and the purine bases are responsible for the creation of macropores due to hydrogen bonding with the silanol groups of the matrix. In a confined environment, the interactions are much stronger for the coencapsulated pair guanine complex. While adenine only establishes hydrogen bonds or van der Waals interactions with the complex, guanine bonds covalently to Ru by one N atom of the imidazole ring, which becomes strongly perturbed, resulting in a deformation of the complex geometry.