title: 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 TiO4N2core. 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 by1H NMR spectroscopy. For the conditions tested (6 mM, DMSO-d6/D2O: 8/1), a rather good stability with t1/2ranging 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 IC50ranging 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)2fragment. Frontier orbitals obtained by DFT calculations permit us to explain this fluorescence quenching.
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Georges
authors.initials: G
authors.lastname: Khalil
authors.affiliation: Laboratoire des "Mécanismes moléculaires de la réponse au stress et pathologies", Inserm U1113 3 avenue Molière, 67200, Strasbourg, France and Département Cancer, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67200 Strasbourg, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Orvain
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Lu
authors.initials: L
authors.lastname: Fang
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Barloy
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Chaumont
authors.affiliation: Laboratoire des "Mécanismes moléculaires de la réponse au stress et pathologies", Inserm U1113 3 avenue Molière, 67200, Strasbourg, France and Département Cancer, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, 67200 Strasbourg, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Gaiddon
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Henry
authors.affiliation: Laboratoire de Tectonique Moléculaire, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kyritsakas
authors.affiliation: Laboratoire de Chimie Moléculaire de l'Etat Solide, UMR 7140 UDS-CNRS, Université de Strasbourg, 4 rue Blaise Pascal, F-67000 Strasbourg, France. mobian@unistra.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mobian
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014025:Titanium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D008024:Ligands; D011743:Pyrimidines; D014025:Titanium