Preface Free

The importance of metals in biology and medicine has grown exponentially since the emergence, in the early 1980s, of the scientific discipline once known as Inorganic Biochemistry or Bioinorganic Chemistry, which is now designated as Biological Inorganic Chemistry (BIC). Since the first International BIC Conference (ICBIC) in Florence in 1983, the role of metals in medicine has never been far from the programme. However, metals, even when they are essential, can be toxic, as can a number of non-essential metals, often referred to as ‘heavy metals’. As Paracelsus pointed out in the 1500 s, anything can be toxic, only dependent on the dose and, while in the case of essential metals toxicity is associated with excessive accumulation of the metal ion, often in specific organs, tissues or cell types, non-essential metal ions become toxic when a particular threshold concentration of the metal ion is exceeded.

As we point out in this latest contribution to the RSC Metallobiology series, in very many clinical situations, the only realistic and appropriate therapeutic option is to administer a specific metal chelator which can remove the metal excess. For essential metals, the aim is to restore the perturbed metal ion homeostasis, whereas for non-essential metal ions the objective is to remove the ‘xenometal’ (my apologies for this literary extravaganza).

We begin with an introductory chapter on metal toxicity, by both essential and non-essential metal ions, which is followed by a chapter reviewing the principles involved in the design of metal chelates. The removal of heavy metals by chelation therapy is then reviewed, followed by chapters on the use of iron chelators in the treatment of transfusional iron overload and their potential in the treatment of neurodegenerative diseases where iron loading in specific brain regions involved in the particular disease highlights the need to target iron chelation to specific locations. Then, the development of octadentate chelators for selective complexation of actinides, which would be absolutely essential in the unthinkable scenario of the terrorist use of a ‘dirty bomb’, is cogently reviewed (representing a totally different level of chelation therapy). The concluding chapters detail the non-invasive techniques which are being increasingly developed for the evaluation of iron overload and their use in diagnostic imaging.

We hope that this volume will help in the search for appropriate therapeutic measures to deal with the complex problems of metal toxicity.

Robert R. Crichton, Roberta J. Ward and Robert C. Hider