Complexes of salicylaldehyde acylhydrazones: Cytotoxicity, QSAR and crystal structure of the sterically hindered t-butyl dimer

A series of acylhydrazones of salicylaldehyde and their transition metal co mplexes, predominantly copper(II), have been prepared and characterized. Th e crystal structure of the Cu(II) complex of the sterically hindered t-buty l derivative contains a phenolate bridged dimer with the ligand coordinated as a tridentate moiety. QSAR analyses of the cytotoxicity of the chelators and their Cu(TI) complexes reveals that solubility is the dominant factor for activity. Compounds display a maximum with respect to lipophilicity, al lowing optimization of the bioactivity for both the ligands and their compl exes. Copper complexes are significantly more cytotoxic than the metal-free ligands and complexes of other metals: Cu > Ni > Zn=Mn > Fe=Cr > Co. (C) 1 998 Elsevier Science Inc. All rights reserved.