title: Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand.
abstract: The reactivity, cytotoxic studies and hydrolytic behaviour of diamine bis(phenolate) titanium complexes are reported. The reactions of [Ti((tBu2)O2NN')Cl]2(μ-O) (1) with LiO(I)Pr or HO(I)Pr in the presence of NEt3, aiming at the synthesis of the alkoxido derivative of 1 led to no reaction or to the synthesis of the monomeric complex [Ti((tBu2)O2NN')(O(i)Pr)2] (3), respectively. A small amount of the alkoxidotitanium dimer [Ti((tBu2)O2NN')(O(i)Pr)]2(μ-O) (2) crystallized out of a solution of 3 and DFT calculations showed that the transformation of 1 into 3 is a thermodynamically favorable process in the presence of a base (NEt3) (ΔG = -14.7 kcal mol(-1)). 2 was quantitatively obtained through the direct reaction of the ligand precursor H2((tBu2)O2NN') with titanium tetra(isopropoxido). Further reaction of 2 with an excess of TMSCl was revealed to be the most suitable method for the preparation of [Ti((tBu2)O2NN')Cl2] (4). 1 and 3 disclosed cytotoxic activity towards HeLa, Fem-x, MDA-MB-361 and K562 cells and 1 exhibited moderate binding affinity to FS-DNA. (1)H NMR hydrolysis studies attested the fast decomposition of 4 in the presence of D2O. The hydrolysis of 3 is slower and proceeds through the formation of [Ti((tBu2)O2NN')(OH)]2(μ-O) (5) that was crystallographically characterized. Upon D2O addition 1 immediately forms complex new species, stable in solution for long periods (weeks).
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. soniabarroso@ist.utl.pt santiago.gomez@urjc.es.
authors.forename: Sónia
authors.initials: S
authors.lastname: Barroso
authors.forename: Ana M
authors.initials: AM
authors.lastname: Coelho
authors.forename: Santiago
authors.initials: S
authors.lastname: Gómez-Ruiz
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Calhorda
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Zižak
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
authors.forename: Ana M
authors.initials: AM
authors.lastname: Martins
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D003959:Diamines / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D010636:Phenols / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003959:Diamines; D008024:Ligands; D010636:Phenols; D014025:Titanium