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).

Heptacoordinate Heteroleptic Salan (ONNO) and Thiosalan (OSSO) Titanium(IV) Complexes: Investigation of Stability and Cytotoxicity

“…A closer inspection of the different spectra recorded during more than 200 h reveals that at any given pH all absorption bands are decreasing simultaneously without any noticeable shift toward a different wavelength which might have pointed to the formation of a (transient) intermediate. 22,40 The stability at lowest and neutral pH is with a half-life of around 6 days remarkably high for a titanium(IV) species and exceeds our standard incubation time more than 3-fold. At pH* 12.1, [L 1 Ti(dipic) 1 ] is decomposing slightly faster, but with a half-life of 50 h it is still highly resistant.…”

Homoleptic Ti[ONO]2 type complexes of amino‐acid‐tethered phenolato Schiff‐base ligands: Synthesis, characterization, time‐resolved fluorescence spectroscopy, and cytotoxicity against ovarian and colon cancer cells

“…[28] The complexes of this class exhibited in vitro and in vivo cytotoxicity toward cancer cells and relatively high hydrolytic stability, and were therefore widely explored. [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] Further stabilization was achieved upon the employment of hexadentate derivatives of the phenolato ligands, leading to highly cytotoxic complexes that were stable for weeks in water. [34,[48][49][50][51][52] These observations, along with other reports of inert Ti(IV) complexes with anticancer properties, [53][54][55] indicate that the labile ligands are not required for antiproliferative effects.…”

Well-defined Ti4 pre-catalysts for the ring-opening polymerisation of lactide

“…Finally, the carboxylate could also bridge to other metal centres leading to expansion of the metal complex into an aggregate. 32 Herein, we present the synthesis, characterisation and design of a robust, air-and water-stable, tetrametallic titanium catalyst for use in the ring-opening polymerisation of rac-lactide. Scheme 1.…”