Abstract
Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its FeIII complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to FeIII in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH–H)2]+ shows that the trivalent oxidation state is dominant over a wide potential range and that the FeII analogue is not a stable form of this complex. The fact that [Fe(NIH–H)2]+ cannot cycle between the FeII and FeIII states suggests that the production of toxic free-radical species, e.g. OH. or O2 . –, is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of FeIII to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its FeIII complex are discussed in the context of understanding its anti-tumour activity.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 12 November 1998 / Accepted: 9 February 1999
Rights and permissions
About this article
Cite this article
Richardson, D., Bernhardt, P. Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity. JBIC 4, 266–273 (1999). https://doi.org/10.1007/s007750050312
Issue Date:
DOI: https://doi.org/10.1007/s007750050312