Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand.

The reactivity, cytotoxic studies and hydrolytic behaviour of diamine bis(phenolate) titanium complexes are reported. The reactions of [Ti(^tBu₂O₂NN')Cl]₂(μ-O) (1) with LiOⁱPr or HOⁱPr 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(^tBu₂O₂NN')(OⁱPr)₂] (3), respectively. A small amount of the alkoxidotitanium dimer [Ti-(^tBu₂O₂NN')(OⁱPr)]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) (∆G = -14.7 kcal mol^-1). 2 was quantitatively obtained through the direct reaction of the ligand precursor H₂(^tBu₂O₂NN') 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(^tBu₂O₂NN')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. ¹H 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(^tBu₂O₂NN')(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). [ABSTRACT FROM AUTHOR]