Ti^IV complexes of branched diamine bis(phenolato) ligands: Hydrolysis and cytotoxicity

Six Ti^IV complexes of branched diamine bis(phenolato) ligands that feature a pendant donor side arm with different aromatic and N-substitutions were synthesized and their hydrolytic stability and cytotoxicity were investigated as closely related analogues to the highly active and stable salan Ti^IV complexes [salan = N,Na′-bis(o-hydroxybenzyl)-1,2- diaminoethane]. Although the C_s-symmetrical complexes include binding of the side-arm N donor to the metal as analyzed crystallographically, thus making them highly similar in coordination features to the C₂- symmetrical salan complexes, they exhibit poor hydrolytic stability, presumably due to higher flexibility in binding of the side arm in solution. Complexes of alkyl aromatic substituents, both N-methylated and N-ethylated, with varying steric constraints demonstrated poor cytotoxicity. In contrast, ortho-halogenation, although it does not affect hydrolytic stability, substantially enhances the cytotoxicity towards colon HT-29 and ovarian OVCAR-1 cells. The cytotoxicity and hydrolysis of Ti^IV complexes of branched diamine bis(phenolato) ligands are reported. Alkylated complexes exhibit poor stability presumably due to weaker binding of the side arm, with negligible cytotoxicity. In contrast, ortho-halogenated complexes, although hydrolytically unstable, demonstrate marked cytotoxicity.