Influence of the Steric Bulk and Solvent on the Photoreactivityof Ruthenium Polypyridyl Complexes Coordinated to l-Proline

摘要

Ruthenium polypyridyl complexes are good candidates for photoactivated chemotherapy (PACT) provided that they are stable in the dark but efficiently photosubstitute one of their ligands. Here the use of the natural amino acid l-proline as a protecting ligand for ruthenium-based PACT compounds is investigated in the series of complexes Λ-[Ru(bpy)2(l-prol)]PF6 ([>1a]PF6; bpy = 2,2′-bipyridine and l-prol = l-proline), Λ-[Ru(bpy)(dmbpy)(l-prol)]PF6 ([>2a]PF6 and [>2b]PF6; dmbpy = 6,6′-dimethyl-2,2′-bipyridine), and Λ-[Ru(dmbpy)2(l-prol)]PF6 ([>3a]PF6). The synthesis of the tris-heteroleptic complex bearing the dissymmetric proline ligand yielded only two of the four possible regioisomers, called [>2a]PF6 and [>2b]PF6. Both isomers were isolated and characterized by a combination of spectroscopy and density functional theory calculations. The photoreactivity of all four complexes [>1a]PF6, [>2a]PF6, [>2b]PF6, and [>3a]PF6 was studied in water (H2O) and acetonitrile (MeCN) using UV–vis spectroscopy, circular dichroism spectroscopy, mass spectrometry, and ¹H NMR spectroscopy. In H₂O, upon visible-light irradiation in the presence of oxygen, no photosubstitution took place,but the amine of complex [>1a]PF₆ was photooxidizedto an imine. Contrary to expectations, enhancing the steric strainby the addition of two ([>2b]PF₆) or four ([>3a]PF₆) methyl substituents did not lead, in phosphate-bufferedsaline (PBS), to ligand photosubstitution. However, it prevented photoxidation,probably as a consequence of the electron-donating effect of the methylsubstituents. In addition, whereas [>2b]PF₆ was photostable in PBS, [>2a]PF₆ quantitativelyisomerized to [>2b]PF₆ upon light irradiation.In pure MeCN, [>2a]PF₆ and [>3a]PF₆ showed non-selective photosubstitution of both the l-proline and dmbpy ligands, whereas the non-strained complex[>1a]PF₆ was photostable. Finally, in H₂O–MeCN mixtures, [>3a]PF₆ showedselective photosubstitution of l-proline, thus demonstratingthe active role played by the solvent on the photoreactivity of thisseries of complexes. The role of the solvent polarity and coordinationproperties on the photochemical properties of polypyridyl complexesis discussed.