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).