Monomeric Ti(iv)-based complexes incorporating luminescent nitrogen ligands: synthesis, structural characterization, emission spectroscopy and cytotoxic activities

Abstract

This manuscript describes the synthesis of a series of neutral titanium(IV) monomeric complexes constructed around a TiO₄N₂ core. The two nitrogen atoms that compose the coordination sphere of the metallic center belong to 2,2′-bipyrimidine ligands homo-disubstituted in the 4 and 4′ positions by methyl (2a), phenylvinyl (2b), naphthylvinyl (2c) or anthrylvinyl (2d) groups. The crystal structures of these complexes named [Ti(1)₂(2a)], [Ti(1)₂(2b)], [Ti(1)₂(2c)] and [Ti(1)₂(2d)] (where 1 is a 2,2′-biphenolato ligand substituted in the 6 and 6′ positions by phenyl groups) are reported. The hydrolytic stability of the four complexes is evaluated by monitoring the evolution of the free 2a–d signals by ¹H NMR spectroscopy. For the conditions tested (6 mM, DMSO-d₆/D₂O: 8/1), a rather good stability with t_1/2 ranging from 180 to 300 min is determined for the complexes. In the presence of an acid (DCl), the hydrolysis of [Ti(1)₂(2a)] is faster than without an acid. The cytotoxic activity against gastric cancer cells of the titanium-based compounds and the free disubstituted 2,2′-bipyrimidine ligands is tested, showing IC₅₀ ranging from 6.2 ± 1.2 μM to 274 ± 56 μM. The fluorescence studies of the ligands 2a–d, and the complexes [Ti(1)₂(2a–d)] reveal an important fluorescence loss of the ligands 2c and 2d upon coordination with the Ti(1)₂ fragment. Frontier orbitals obtained by DFT calculations permit us to explain this fluorescence quenching.