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

Abstract

Seven heptacoordinate titanium(IV) complexes were synthesized based on the concept of hetero-bis-chelate stabilization of salan (ONNO) and thiosalan (OSSO) titanium(IV)alkoxides with 2,6-pyridinedicarboxylic acid (dipic) and derivatives thereof. The resulting compounds were investigated in a solid by X-ray diffraction and in solution by NMR spectroscopy. A thiosalan (OSSO) titanium(IV) complex could be isolated and its conformational stabilization by dipic was shown by (1)H NMR spectroscopy to lead to nonfluxional behavior even at room temperature. The stability of selected complexes was assessed at pH 1.9, 6.8, and 12.1 by an UV-vis monitored hydrolysis study with >5 Mio. equivalents of water. Even at pH 12.1 [L(1)Ti(dipic)(1)] showed t1/2 of more than 2 days. The cytotoxicity of all compounds was investigated in two human carcinoma cell lines. IC50-values in the range of cisplatin were achieved by all tested compounds except for [L(4)Ti(dipic)(1)], which was proven to be nontoxic. The functionalization of dipic was thus well tolerated and did neither interfere with the stability nor the cytotoxicity of the heteroleptic complexes.